Impaired Regeneration Potential in Urinary Stem Cells Diagnosed from the Patients with Diabetic Nephropathy
Identifieur interne : 000778 ( Ncbi/Merge ); précédent : 000777; suivant : 000779Impaired Regeneration Potential in Urinary Stem Cells Diagnosed from the Patients with Diabetic Nephropathy
Auteurs : Geng Xiong [République populaire de Chine, États-Unis] ; Weiqing Tang [République populaire de Chine] ; Deying Zhang [États-Unis, République populaire de Chine] ; David He [République populaire de Chine] ; Guanghui Wei [République populaire de Chine] ; Antony Atala [États-Unis] ; Xing-Jie Liang [République populaire de Chine] ; Anthony J. Bleyer [États-Unis] ; Michael E. Bleyer [États-Unis] ; Jie Yu [États-Unis] ; Joseph A. Aloi [États-Unis] ; Jian-Xing Ma [États-Unis] ; Cristina M. Furdui [États-Unis] ; Yuanyuan Zhang [États-Unis]Source :
- Theranostics [ 1838-7640 ] ; 2019.
Abstract
Stem cells present in urine possess regenerative capacity to repair kidney injury. However, the unique characteristics of urinary stem cells (USC) from patients with diabetic nephropathy (d-USC) are unknown. The goal of this study was to investigate stemness properties in cell phenotype and regenerative potential of d-USC, compared to USC from healthy individuals.
Url:
DOI: 10.7150/thno.34050
PubMed: 31281543
PubMed Central: 6592174
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NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Weiqing" sort="Tang, Weiqing" uniqKey="Tang W" first="Weiqing" last="Tang">Weiqing Tang</name><affiliation wicri:level="3"><nlm:aff id="A2">The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Deying" sort="Zhang, Deying" uniqKey="Zhang D" first="Deying" last="Zhang">Deying Zhang</name><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="He, David" sort="He, David" uniqKey="He D" first="David" last="He">David 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first="Antony" last="Atala">Antony Atala</name><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Xing Jie" sort="Liang, Xing Jie" uniqKey="Liang X" first="Xing-Jie" last="Liang">Xing-Jie Liang</name><affiliation wicri:level="3"><nlm:aff id="A5">Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Bleyer, Anthony J" sort="Bleyer, Anthony J" uniqKey="Bleyer A" first="Anthony J." last="Bleyer">Anthony J. Bleyer</name><affiliation wicri:level="1"><nlm:aff id="A6">Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Bleyer, Michael E" sort="Bleyer, Michael E" uniqKey="Bleyer M" first="Michael E." last="Bleyer">Michael E. Bleyer</name><affiliation wicri:level="1"><nlm:aff id="A6">Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Jie" sort="Yu, Jie" uniqKey="Yu J" first="Jie" last="Yu">Jie Yu</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Aloi, Joseph A" sort="Aloi, Joseph A" uniqKey="Aloi J" first="Joseph A." last="Aloi">Joseph A. Aloi</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Jian Xing" sort="Ma, Jian Xing" uniqKey="Ma J" first="Jian-Xing" last="Ma">Jian-Xing Ma</name><affiliation wicri:level="1"><nlm:aff id="A9">Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK</wicri:regionArea><wicri:noRegion>OK</wicri:noRegion></affiliation></author><author><name sortKey="Furdui, Cristina M" sort="Furdui, Cristina M" uniqKey="Furdui C" first="Cristina M." last="Furdui">Cristina M. Furdui</name><affiliation wicri:level="1"><nlm:aff id="A10">Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yuanyuan" sort="Zhang, Yuanyuan" uniqKey="Zhang Y" first="Yuanyuan" last="Zhang">Yuanyuan Zhang</name><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno 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first="Geng" last="Xiong">Geng Xiong</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatric Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pediatric Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan</wicri:regionArea><wicri:noRegion>Sichuan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Weiqing" sort="Tang, Weiqing" uniqKey="Tang W" first="Weiqing" last="Tang">Weiqing Tang</name><affiliation wicri:level="3"><nlm:aff id="A2">The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Deying" sort="Zhang, Deying" uniqKey="Zhang D" first="Deying" last="Zhang">Deying Zhang</name><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="He, David" sort="He, David" uniqKey="He D" first="David" last="He">David He</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Guanghui" sort="Wei, Guanghui" uniqKey="Wei G" first="Guanghui" last="Wei">Guanghui Wei</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing</wicri:regionArea><wicri:noRegion>Chongqing</wicri:noRegion></affiliation></author><author><name sortKey="Atala, Antony" sort="Atala, Antony" uniqKey="Atala A" first="Antony" last="Atala">Antony Atala</name><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Liang, Xing Jie" sort="Liang, Xing Jie" uniqKey="Liang X" first="Xing-Jie" last="Liang">Xing-Jie Liang</name><affiliation wicri:level="3"><nlm:aff id="A5">Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Bleyer, Anthony J" sort="Bleyer, Anthony J" uniqKey="Bleyer A" first="Anthony J." last="Bleyer">Anthony J. Bleyer</name><affiliation wicri:level="1"><nlm:aff id="A6">Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Bleyer, Michael E" sort="Bleyer, Michael E" uniqKey="Bleyer M" first="Michael E." last="Bleyer">Michael E. Bleyer</name><affiliation wicri:level="1"><nlm:aff id="A6">Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Jie" sort="Yu, Jie" uniqKey="Yu J" first="Jie" last="Yu">Jie Yu</name><affiliation wicri:level="1"><nlm:aff id="A7">Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Aloi, Joseph A" sort="Aloi, Joseph A" uniqKey="Aloi J" first="Joseph A." last="Aloi">Joseph A. Aloi</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Jian Xing" sort="Ma, Jian Xing" uniqKey="Ma J" first="Jian-Xing" last="Ma">Jian-Xing Ma</name><affiliation wicri:level="1"><nlm:aff id="A9">Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK</wicri:regionArea><wicri:noRegion>OK</wicri:noRegion></affiliation></author><author><name sortKey="Furdui, Cristina M" sort="Furdui, Cristina M" uniqKey="Furdui C" first="Cristina M." last="Furdui">Cristina M. Furdui</name><affiliation wicri:level="1"><nlm:aff id="A10">Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yuanyuan" sort="Zhang, Yuanyuan" uniqKey="Zhang Y" first="Yuanyuan" last="Zhang">Yuanyuan Zhang</name><affiliation wicri:level="1"><nlm:aff id="A3">Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC</wicri:regionArea><wicri:noRegion>NC</wicri:noRegion></affiliation></author></analytic><series><title level="j">Theranostics</title><idno type="eISSN">1838-7640</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Stem cells present in urine possess regenerative capacity to repair kidney injury. However, the unique characteristics of urinary stem cells (USC) from patients with diabetic nephropathy (d-USC) are unknown. The goal of this study was to investigate stemness properties in cell phenotype and regenerative potential of d-USC, compared to USC from healthy individuals.</p><p><bold>Methods</bold>: Thirty-six urine samples collected from patients (n=12, age range 60-75 years) with diabetic nephropathy (stages 3-4 stage chronic kidney disease [CKD]) were compared with 30 urine samples from healthy age-matched donors (n=10, age range 60-74 years).</p><p><bold>Results</bold>: There were approximately six times as many cells in urine samples from patients with diabetic nephropathy, including twice as many USC clones as healthy donors. However, approximately 70% of d-USC had weaker regenerative capacity as assessed by cell proliferation, less secretion of paracrine factors, weaker telomerase activity, and lower renal tubular epithelial differentiation potential compared to healthy controls. In addition, the levels of inflammatory factors (IL-1β and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (<italic>p<0.01</italic>). Protein levels of autophagy marker (LC3-II) and mTOR signaling molecules (p-mTOR/mTOR, p-Raptor/Raptor and p-S6K1) were significantly lower in patient with diabetic nephropathy (<italic>p<0.01</italic>). Nevertheless, up to 30% of d-USC possessed similar regenerative capacity as USC from healthy donors.</p><p><bold>Conclusions</bold>: Regenerative performance of most d-USC was significantly lower than normal controls. Understanding the specific changes in d-USC regeneration capability will help elucidate the pathobiology of diabetic nephropathy and lead to prevent USC from diabetic insults, recover the stemness function and also identify novel biomarkers to predict progression of this chronic kidney disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Reeves, Wb" uniqKey="Reeves W">WB Reeves</name></author><author><name sortKey="Andreoli, Te" uniqKey="Andreoli T">TE Andreoli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ritz, E" uniqKey="Ritz E">E Ritz</name></author><author><name sortKey="Orth, Sr" uniqKey="Orth S">SR Orth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Mcneill, E" uniqKey="Mcneill E">E McNeill</name></author><author><name sortKey="Tian, H" uniqKey="Tian H">H Tian</name></author><author><name sortKey="Soker, S" uniqKey="Soker S">S Soker</name></author><author><name sortKey="Andersson, Ke" uniqKey="Andersson K">KE Andersson</name></author><author><name sortKey="Yoo, Jj" uniqKey="Yoo J">JJ Yoo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bharadwaj, S" uniqKey="Bharadwaj S">S Bharadwaj</name></author><author><name sortKey="Liu, G" uniqKey="Liu G">G Liu</name></author><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name></author><author><name sortKey="Wu, R" uniqKey="Wu R">R Wu</name></author><author><name sortKey="Yang, B" uniqKey="Yang B">B Yang</name></author><author><name sortKey="He, T" uniqKey="He T">T He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Rp" uniqKey="Wu R">RP Wu</name></author><author><name sortKey="Liu, G" uniqKey="Liu G">G Liu</name></author><author><name sortKey="Shi, Ya" uniqKey="Shi Y">YA Shi</name></author><author><name sortKey="Bharadwaj, S" uniqKey="Bharadwaj S">S Bharadwaj</name></author><author><name sortKey="Atala, A" uniqKey="Atala A">A Atala</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, D" uniqKey="Zhang D">D Zhang</name></author><author><name sortKey="Wei, G" uniqKey="Wei G">G Wei</name></author><author><name sortKey="Li, P" uniqKey="Li P">P Li</name></author><author><name sortKey="Zhou, X" uniqKey="Zhou X">X Zhou</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, D" uniqKey="Qin D">D Qin</name></author><author><name sortKey="Long, T" uniqKey="Long T">T Long</name></author><author><name sortKey="Deng, J" uniqKey="Deng J">J Deng</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herberts, Ca" uniqKey="Herberts C">CA Herberts</name></author><author><name sortKey="Kwa, Ms" uniqKey="Kwa M">MS Kwa</name></author><author><name sortKey="Hermsen, Hp" uniqKey="Hermsen H">HP Hermsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lazzeri, E" uniqKey="Lazzeri E">E Lazzeri</name></author><author><name sortKey="Ronconi, E" uniqKey="Ronconi E">E Ronconi</name></author><author><name sortKey="Angelotti, Ml" uniqKey="Angelotti M">ML Angelotti</name></author><author><name sortKey="Peired, A" uniqKey="Peired A">A Peired</name></author><author><name sortKey="Mazzinghi, B" uniqKey="Mazzinghi B">B Mazzinghi</name></author><author><name sortKey="Becherucci, F" uniqKey="Becherucci F">F Becherucci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Ma, W" uniqKey="Ma W">W Ma</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B Liu</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Chu, J" uniqKey="Chu J">J Chu</name></author><author><name sortKey="Xiong, G" uniqKey="Xiong G">G Xiong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tran, C" uniqKey="Tran C">C Tran</name></author><author><name sortKey="Tangada, A" uniqKey="Tangada A">A Tangada</name></author><author><name sortKey="Yi, H" uniqKey="Yi H">H Yi</name></author><author><name sortKey="Balog, B" uniqKey="Balog B">B Balog</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Damaser, M" uniqKey="Damaser M">M Damaser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Jn" uniqKey="Lee J">JN Lee</name></author><author><name sortKey="Chun, Sy" uniqKey="Chun S">SY Chun</name></author><author><name sortKey="Lee, Hj" uniqKey="Lee H">HJ Lee</name></author><author><name sortKey="Jang, Yj" uniqKey="Jang Y">YJ Jang</name></author><author><name sortKey="Choi, Sh" uniqKey="Choi S">SH Choi</name></author><author><name sortKey="Kim, Dh" uniqKey="Kim D">DH Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author><author><name sortKey="Xing, F" uniqKey="Xing F">F Xing</name></author><author><name sortKey="Peng, J" uniqKey="Peng J">J Peng</name></author><author><name sortKey="Peng, K" uniqKey="Peng K">K Peng</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dong, X" uniqKey="Dong X">X Dong</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T Zhang</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name></author><author><name sortKey="Zhu, J" uniqKey="Zhu J">J Zhu</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, C Y" uniqKey="Chen C">C-Y Chen</name></author><author><name sortKey="Rao, S S" uniqKey="Rao S">S-S Rao</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L Ren</name></author><author><name sortKey="Hu, X K" uniqKey="Hu X">X-K Hu</name></author><author><name sortKey="Tan, Y J" uniqKey="Tan Y">Y-J Tan</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Zheng, T" uniqKey="Zheng T">T Zheng</name></author><author><name sortKey="Han, D" uniqKey="Han D">D Han</name></author><author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name></author><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ouyang, B" uniqKey="Ouyang B">B Ouyang</name></author><author><name sortKey="Sun, X" uniqKey="Sun X">X Sun</name></author><author><name sortKey="Han, D" uniqKey="Han D">D Han</name></author><author><name sortKey="Chen, S" uniqKey="Chen S">S Chen</name></author><author><name sortKey="Yao, B" uniqKey="Yao B">B Yao</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Han, Jw" uniqKey="Han J">JW Han</name></author><author><name sortKey="Sin, My" uniqKey="Sin M">MY Sin</name></author><author><name sortKey="Yoon, Ys" uniqKey="Yoon Y">YS Yoon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klinkhammer, Bm" uniqKey="Klinkhammer B">BM Klinkhammer</name></author><author><name sortKey="Kramann, R" uniqKey="Kramann R">R Kramann</name></author><author><name sortKey="Mallau, M" uniqKey="Mallau M">M Mallau</name></author><author><name sortKey="Makowska, A" uniqKey="Makowska A">A Makowska</name></author><author><name sortKey="Van Roeyen, Cr" uniqKey="Van Roeyen C">CR van Roeyen</name></author><author><name sortKey="Rong, S" uniqKey="Rong S">S Rong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaw, Lc" uniqKey="Shaw L">LC Shaw</name></author><author><name sortKey="Neu, Mb" uniqKey="Neu M">MB Neu</name></author><author><name sortKey="Grant, Mb" uniqKey="Grant M">MB Grant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ko, Ki" uniqKey="Ko K">KI Ko</name></author><author><name sortKey="Coimbra, Ls" uniqKey="Coimbra L">LS Coimbra</name></author><author><name sortKey="Tian, C" uniqKey="Tian C">C Tian</name></author><author><name sortKey="Alblowi, J" uniqKey="Alblowi J">J Alblowi</name></author><author><name sortKey="Kayal, Ra" uniqKey="Kayal R">RA Kayal</name></author><author><name sortKey="Einhorn, Ta" uniqKey="Einhorn T">TA Einhorn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, M" uniqKey="Zhu M">M Zhu</name></author><author><name sortKey="He, X" uniqKey="He X">X He</name></author><author><name sortKey="Wang, Xh" uniqKey="Wang X">XH Wang</name></author><author><name sortKey="Qiu, W" uniqKey="Qiu W">W Qiu</name></author><author><name sortKey="Xing, W" uniqKey="Xing W">W Xing</name></author><author><name sortKey="Guo, W" uniqKey="Guo W">W Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hazra, S" uniqKey="Hazra S">S Hazra</name></author><author><name sortKey="Jarajapu, Yp" uniqKey="Jarajapu Y">YP Jarajapu</name></author><author><name sortKey="Stepps, V" uniqKey="Stepps V">V Stepps</name></author><author><name sortKey="Caballero, S" uniqKey="Caballero S">S Caballero</name></author><author><name sortKey="Thinschmidt, Js" uniqKey="Thinschmidt J">JS Thinschmidt</name></author><author><name sortKey="Sautina, L" uniqKey="Sautina L">L Sautina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levey, As" uniqKey="Levey A">AS Levey</name></author><author><name sortKey="Coresh, J" uniqKey="Coresh J">J Coresh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pahl, Hl" uniqKey="Pahl H">HL Pahl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montane, J" uniqKey="Montane J">J Montane</name></author><author><name sortKey="Cadavez, L" uniqKey="Cadavez L">L Cadavez</name></author><author><name sortKey="Novials, A" uniqKey="Novials A">A Novials</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abed, A" uniqKey="Abed A">A Abed</name></author><author><name sortKey="Toubas, J" uniqKey="Toubas J">J Toubas</name></author><author><name sortKey="Kavvadas, P" uniqKey="Kavvadas P">P Kavvadas</name></author><author><name sortKey="Authier, F" uniqKey="Authier F">F Authier</name></author><author><name sortKey="Cathelin, D" uniqKey="Cathelin D">D Cathelin</name></author><author><name sortKey="Alfieri, C" uniqKey="Alfieri C">C Alfieri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toubas, J" uniqKey="Toubas J">J Toubas</name></author><author><name sortKey="Beck, S" uniqKey="Beck S">S Beck</name></author><author><name sortKey="Pageaud, Al" uniqKey="Pageaud A">AL Pageaud</name></author><author><name sortKey="Huby, Ac" uniqKey="Huby A">AC Huby</name></author><author><name sortKey="Mael Ainin, M" uniqKey="Mael Ainin M">M Mael-Ainin</name></author><author><name sortKey="Dussaule, Jc" uniqKey="Dussaule J">JC Dussaule</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soo, Jy" uniqKey="Soo J">JY Soo</name></author><author><name sortKey="Jansen, J" uniqKey="Jansen J">J Jansen</name></author><author><name sortKey="Masereeuw, R" uniqKey="Masereeuw R">R Masereeuw</name></author><author><name sortKey="Little, Mh" uniqKey="Little M">MH Little</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakamura, T" uniqKey="Nakamura T">T Nakamura</name></author><author><name sortKey="Ushiyama, C" uniqKey="Ushiyama C">C Ushiyama</name></author><author><name sortKey="Suzuki, S" uniqKey="Suzuki S">S Suzuki</name></author><author><name sortKey="Hara, M" uniqKey="Hara M">M Hara</name></author><author><name sortKey="Shimada, N" uniqKey="Shimada N">N Shimada</name></author><author><name sortKey="Ebihara, I" uniqKey="Ebihara I">I Ebihara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sureshbabu, A" uniqKey="Sureshbabu A">A Sureshbabu</name></author><author><name sortKey="Ryter, Sw" uniqKey="Ryter S">SW Ryter</name></author><author><name sortKey="Choi, Me" uniqKey="Choi M">ME Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denu, Ra" uniqKey="Denu R">RA Denu</name></author><author><name sortKey="Hematti, P" uniqKey="Hematti P">P Hematti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bigarella, Cl" uniqKey="Bigarella C">CL Bigarella</name></author><author><name sortKey="Liang, R" uniqKey="Liang R">R Liang</name></author><author><name sortKey="Ghaffari, S" uniqKey="Ghaffari S">S Ghaffari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lieberthal, W" uniqKey="Lieberthal W">W Lieberthal</name></author><author><name sortKey="Levine, Js" uniqKey="Levine J">JS Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, P" uniqKey="Liu P">P Liu</name></author><author><name sortKey="Liu, K" uniqKey="Liu K">K Liu</name></author><author><name sortKey="Gu, H" uniqKey="Gu H">H Gu</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Gong, J" uniqKey="Gong J">J Gong</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hillis, Gs" uniqKey="Hillis G">GS Hillis</name></author><author><name sortKey="Duthie, La" uniqKey="Duthie L">LA Duthie</name></author><author><name sortKey="Brown, Pa" uniqKey="Brown P">PA Brown</name></author><author><name sortKey="Simpson, Jg" uniqKey="Simpson J">JG Simpson</name></author><author><name sortKey="Macleod, Am" uniqKey="Macleod A">AM MacLeod</name></author><author><name sortKey="Haites, Ne" uniqKey="Haites N">NE Haites</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sarieddine, Mz" uniqKey="Sarieddine M">MZ Sarieddine</name></author><author><name sortKey="Scheckenbach, Ke" uniqKey="Scheckenbach K">KE Scheckenbach</name></author><author><name sortKey="Foglia, B" uniqKey="Foglia B">B Foglia</name></author><author><name sortKey="Maass, K" uniqKey="Maass K">K Maass</name></author><author><name sortKey="Garcia, I" uniqKey="Garcia I">I Garcia</name></author><author><name sortKey="Kwak, Br" uniqKey="Kwak B">BR Kwak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ey, B" uniqKey="Ey B">B Ey</name></author><author><name sortKey="Eyking, A" uniqKey="Eyking A">A Eyking</name></author><author><name sortKey="Gerken, G" uniqKey="Gerken G">G Gerken</name></author><author><name sortKey="Podolsky, Dk" uniqKey="Podolsky D">DK Podolsky</name></author><author><name sortKey="Cario, E" uniqKey="Cario E">E Cario</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sawai, K" uniqKey="Sawai K">K Sawai</name></author><author><name sortKey="Mukoyama, M" uniqKey="Mukoyama M">M Mukoyama</name></author><author><name sortKey="Mori, K" uniqKey="Mori K">K Mori</name></author><author><name sortKey="Yokoi, H" uniqKey="Yokoi H">H Yokoi</name></author><author><name sortKey="Koshikawa, M" uniqKey="Koshikawa M">M Koshikawa</name></author><author><name sortKey="Yoshioka, T" uniqKey="Yoshioka T">T Yoshioka</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Theranostics</journal-id><journal-id journal-id-type="iso-abbrev">Theranostics</journal-id><journal-id journal-id-type="publisher-id">thno</journal-id><journal-title-group><journal-title>Theranostics</journal-title></journal-title-group><issn pub-type="epub">1838-7640</issn><publisher><publisher-name>Ivyspring International Publisher</publisher-name><publisher-loc>Sydney</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31281543</article-id><article-id pub-id-type="pmc">6592174</article-id><article-id pub-id-type="doi">10.7150/thno.34050</article-id><article-id pub-id-type="publisher-id">thnov09p4221</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Impaired Regeneration Potential in Urinary Stem Cells Diagnosed from the Patients with Diabetic Nephropathy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Xiong</surname><given-names>Geng</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Tang</surname><given-names>Weiqing</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Deying</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>He</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Wei</surname><given-names>Guanghui</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Atala</surname><given-names>Antony</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Liang</surname><given-names>Xing-Jie</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Bleyer</surname><given-names>Anthony J.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Bleyer</surname><given-names>Michael E.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Yu</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Aloi</surname><given-names>Joseph A.</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Jian-Xing</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Furdui</surname><given-names>Cristina M.</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Yuanyuan</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pediatric Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China</aff><aff id="A2"><label>2</label>The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China</aff><aff id="A3"><label>3</label>Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA</aff><aff id="A4"><label>4</label>Department of Urology, Children Hospital of Chongqing Medical University, Chongqing, China</aff><aff id="A5"><label>5</label>Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, China</aff><aff id="A6"><label>6</label>Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</aff><aff id="A7"><label>7</label>Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, NC, USA</aff><aff id="A8"><label>8</label>Department of Endocrinology, Wake Forest School of Medicine, Winston-Salem, NC, USA</aff><aff id="A9"><label>9</label>Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.</aff><aff id="A10"><label>10</label>Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA</aff><author-notes><corresp id="FNA_envelop">✉ Corresponding author: Yuanyuan Zhang. E-mail: <email>yzhang@wakehealth.edu</email>, Tel: 1-336-713-1189</corresp><fn fn-type="equal" id="FNA_star"><p>* Both authors contribute equally in this study</p></fn><fn fn-type="COI-statement"><p>Competing Interests: The authors have declared that no competing interest exists.</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>31</day><month>5</month><year>2019</year></pub-date><volume>9</volume><issue>14</issue><fpage>4221</fpage><lpage>4232</lpage><history><date date-type="received"><day>12</day><month>2</month><year>2019</year></date><date date-type="accepted"><day>3</day><month>4</month><year>2019</year></date></history><permissions><copyright-statement>© Ivyspring International Publisher</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc/4.0/">https://creativecommons.org/licenses/by-nc/4.0/</ext-link>). See <ext-link ext-link-type="uri" xlink:href="http://ivyspring.com/terms">http://ivyspring.com/terms</ext-link> for full terms and conditions.</license-p></license></permissions><abstract><p>Stem cells present in urine possess regenerative capacity to repair kidney injury. However, the unique characteristics of urinary stem cells (USC) from patients with diabetic nephropathy (d-USC) are unknown. The goal of this study was to investigate stemness properties in cell phenotype and regenerative potential of d-USC, compared to USC from healthy individuals.</p><p><bold>Methods</bold>: Thirty-six urine samples collected from patients (n=12, age range 60-75 years) with diabetic nephropathy (stages 3-4 stage chronic kidney disease [CKD]) were compared with 30 urine samples from healthy age-matched donors (n=10, age range 60-74 years).</p><p><bold>Results</bold>: There were approximately six times as many cells in urine samples from patients with diabetic nephropathy, including twice as many USC clones as healthy donors. However, approximately 70% of d-USC had weaker regenerative capacity as assessed by cell proliferation, less secretion of paracrine factors, weaker telomerase activity, and lower renal tubular epithelial differentiation potential compared to healthy controls. In addition, the levels of inflammatory factors (IL-1β and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (<italic>p<0.01</italic>). Protein levels of autophagy marker (LC3-II) and mTOR signaling molecules (p-mTOR/mTOR, p-Raptor/Raptor and p-S6K1) were significantly lower in patient with diabetic nephropathy (<italic>p<0.01</italic>). Nevertheless, up to 30% of d-USC possessed similar regenerative capacity as USC from healthy donors.</p><p><bold>Conclusions</bold>: Regenerative performance of most d-USC was significantly lower than normal controls. Understanding the specific changes in d-USC regeneration capability will help elucidate the pathobiology of diabetic nephropathy and lead to prevent USC from diabetic insults, recover the stemness function and also identify novel biomarkers to predict progression of this chronic kidney disease.</p></abstract><kwd-group><kwd>diabetic nephropathy</kwd><kwd>urine</kwd><kwd>stem cells</kwd><kwd>renal insufficiency</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><p><bold> Cell morphology, proliferation and cell surface markers of d-USC. (A)</bold> Cell morphology of d-USC was similar to that of USC at the early stage (<italic>p0</italic> to <italic>p3)</italic>, the cell size increased with more vacuoles existed in most d-USC at <italic>p</italic>5, compared to USC with uniform and small size at <italic>p</italic>7. <bold>(B)</bold> Cell proliferation remarkably decreased in d-USC at <italic>p5,</italic> compared to that in USC at <italic>p5</italic>. (<bold>C</bold>) The d-USC at <italic>p</italic>5 expressed positive for mesenchymal stromal cell markers, including CD44, CD73, CD90, and CD105, and negative for the hematopoietic stem cell markers such as CD31, CD34 and CD45, assessed by flow cytometry.</p></caption><graphic xlink:href="thnov09p4221g001"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><p><bold> Normal chromosomes detected in d-USC.</bold> No multi-ploidy or obvious chromosomal rearrangements at metaphase were detected in d-USC at <italic>p5</italic> by Giemsa band karyogamy.</p></caption><graphic xlink:href="thnov09p4221g002"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><p><bold> Telomerase activity in d-USC. (A)</bold> Both d-USC (n=10 patients with DN) and USC clones (n=10 healthy donors) at <italic>p5</italic> showed telomerase positive (A450nm-A690nm > 0.2 units). <bold>(B)</bold> The levels of telomerase activity of d-USC clones showed significantly lower than those of USC (*<italic> p < 0.01</italic>). HEK 293 cells were used as a positive control.</p></caption><graphic xlink:href="thnov09p4221g003"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><p><bold> Levels of Trophic factors secreted from d-USC.</bold> Levels of 32 pro-angiogenic growth factors secreted from d-USC (5×10<sup>5</sup>, <italic>p5</italic>) in vitro were significantly lower than those from USC, analyzed by human angiogenesis array kit, Relative Pixel Density presented as mean ± SD (<italic>p<0.01</italic>). Levels of seven proteins (Angiopoietin-1, Angiostatin/Plasminogen, Coagulation Factor III, Leptin, MIP-1α, Serpin E1, Thrombospondin-1) secreted in d-USC were similar to or higher than those in USC.</p></caption><graphic xlink:href="thnov09p4221g004"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><p><bold> Renal tubular epithelial differentiation of d-USC.</bold> Expression of renal tubular epithelial cell markers (Na/K ATPase, E-Cadherin, AQP-1) in d-USC at <italic>p5</italic> were significantly less compared to that in USC, quantitatively assessed by immunofluorescence staining (<bold>A</bold>) and by Western-blot (n = 6) (<bold>B</bold>). Results were presented as mean ± SD (*<italic>p < 0.01; ** p > 0.05</italic>).</p></caption><graphic xlink:href="thnov09p4221g005"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><p><bold> mTOR signaling pathway in d-USC. (A)</bold> Phosphorylation of mTOR signaling pathway was inhibited in d-USC at <italic>p5</italic>, compare to that in USC. <bold>(B)</bold> Ratios of p-mTOR/total m-TOR, p-Raptor/total Raptor and p-S6K/β-actin in d-USC (n = 10) were significantly lower than those in USC (*<italic>p < 0.01</italic>). Results presented as mean ± SD were quantitatively analyzed by Western blot.</p></caption><graphic xlink:href="thnov09p4221g006"></graphic></fig><fig id="F7" position="float"><label>Figure 7</label><caption><p><bold> Lower autophagic flux in d-USC. (A)</bold> No difference in LC3 expression between d-USC and USC when grew in normal culture medium or medium containing chloroquine for 2 hours, assessed by Western blotting. β-actin served as the loading control. <bold>(B)</bold> Quantification of autophagic flux by calculating the ratio of LC3-II with or without CQ treatment in starvation. Levels of LC3-II in d-USC were significantly lower in d-USC treated in HBSS buffer (starvation for 2 h) and chloroquine (CQ, 10 μM, starvation for 2 h) treatment than those in USC. Data shown are the mean ± SD, n = 6 individual cell clones, <italic>*p < 0.05, **p > 0.05</italic> (Student's t-test).<bold> (C)</bold> Representative transmission electron microscopy (TEM) images showed less autophagic vacuoles (AVs, indicated by short arrowheads) in d-USC with CQ treatment (10 μM, 2 h), compared to those in USC (scale bars, 500 nm).</p></caption><graphic xlink:href="thnov09p4221g007"></graphic></fig><fig id="F8" position="float"><label>Figure 8</label><caption><p><bold> Expression of inflammatory and Oxidative stress markers in d-USC. (A)</bold> Expression of IL-1β in d-USC was significantly higher than that in USC (<italic>at p5</italic>) (* <italic>p < 0.01</italic>), assessed by Western Blot. Data were repeated in 6 independent experiments and shown as mean ± SD. <bold>(B)</bold> Cx43 expression of d-USC (n = 6 individual cell clones) at <italic>p5</italic> was significantly higher than that in USC from healthy donors (n = 6 individual cell clones) (* <italic>p < 0.01</italic>), assessed by Western Blot. Data were repeated in 12 independent experiments and shown as Means ± SD. <bold>(C)</bold> Expression of Nitro-Tyrosine in d-USC (<italic>p5,</italic> n = 6 individual cell clones) showed significantly higher than that in USC (<italic>p</italic>5<italic>,</italic> n = 6 individual cell clones) (* <italic>p < 0.01</italic>), assessed by Western Blot. The data were repeated in 6 independent experiments and shown as means ± SD.</p></caption><graphic xlink:href="thnov09p4221g008"></graphic></fig><fig id="F9" position="float"><label>Figure 9</label><caption><p><bold> Apoptosis and apoptosis-related protein in d-USC. (A)</bold> Marker of apoptosis expressed positive in d-USC at p5 with TUNEL staining (green), compared to that in USC at <italic>p5</italic> 24 hours after seeding at 5 x 10<sup>5</sup> cells/well in a 6-well plate, captured by a fluorescence microscope (400×). Numbers of cells expressed apoptosis‐related marker in d-USC (n = 10 samples) was significantly higher compared to those in USC (n=10 samples) (<italic>*p<0.01</italic>). Data represented mean ± SD. <bold>(B)</bold> The d-USC expressed significantly higher amount of apoptosis-related protein c-cas-3 protein compared to USC (<italic>p5</italic>) samples (*<italic>p<0.01</italic>). Data were presented as mean ± SD, assessed with Western Blot</p></caption><graphic xlink:href="thnov09p4221g009"></graphic></fig><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Total numbers of cells and USC clones in urine from healthy donors and the patients with DN</p></caption><table frame="hsides" rules="groups"><thead valign="top"><tr><th rowspan="1" colspan="1"></th><th rowspan="1" colspan="1">Healthy individuals <italic>(n=10, M ±SD)</italic></th><th rowspan="1" colspan="1">Pts. with DN <italic>(n=12, M±SD)</italic></th></tr></thead><tbody valign="top"><tr><td rowspan="1" colspan="1">Total no. of cells ×10<sup>6</sup> /100ml urine</td><td rowspan="1" colspan="1">0.6 ± 0.1</td><td rowspan="1" colspan="1">4.3 ± 1.0*</td></tr><tr><td rowspan="1" colspan="1">Total no. of live cells ×10<sup>6</sup> /100ml urine</td><td rowspan="1" colspan="1">0.4 ± 0.1</td><td rowspan="1" colspan="1">2.1 ± 0.6**</td></tr><tr><td rowspan="1" colspan="1">Live cell ratio (no. of live cells/total no. of cells)</td><td rowspan="1" colspan="1">66.4 ± 10.9</td><td rowspan="1" colspan="1">50.1 ± 7.9*</td></tr><tr><td rowspan="1" colspan="1">USC initial appearance time (Days)</td><td rowspan="1" colspan="1">4.5 ± 1.0</td><td rowspan="1" colspan="1">7.2 ± 2.1*</td></tr><tr><td rowspan="1" colspan="1">USC clone No. at <italic>p</italic>0/100ml urine</td><td rowspan="1" colspan="1">7.3 ± 2.3</td><td rowspan="1" colspan="1">13.0 ± 3.0*</td></tr><tr><td rowspan="1" colspan="1">><italic>p</italic>5 clone number percentage (%)</td><td rowspan="1" colspan="1">69.2 ± 6.8</td><td rowspan="1" colspan="1">27.1 ± 5.9*</td></tr><tr><td rowspan="1" colspan="1">Population doubling (<italic>p</italic>1-<italic>p</italic>8)</td><td rowspan="1" colspan="1">43.5 ± 2.1</td><td rowspan="1" colspan="1">28.3 ± 3.0*</td></tr><tr><td rowspan="1" colspan="1">Doubling time (hours) (<italic>p</italic>1-<italic>p</italic>5)</td><td rowspan="1" colspan="1">25.1 ± 1.9</td><td rowspan="1" colspan="1">38.4 ± 2.5*</td></tr></tbody></table><table-wrap-foot><fn><p><bold>Abbreviations</bold>: DN: diabetic nephropathy; Pts: patients; No: number</p><p><bold>Note</bold>: *<sup>/</sup>** indicating significant difference in the permeates between healthy donors and patients with DN, *p<0.01; **p<0.05</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xiong, Geng" sort="Xiong, Geng" uniqKey="Xiong G" first="Geng" last="Xiong">Geng Xiong</name></noRegion><name sortKey="He, David" sort="He, David" uniqKey="He D" first="David" last="He">David He</name><name sortKey="Liang, Xing Jie" sort="Liang, Xing Jie" uniqKey="Liang X" first="Xing-Jie" last="Liang">Xing-Jie Liang</name><name sortKey="Tang, Weiqing" sort="Tang, Weiqing" uniqKey="Tang W" first="Weiqing" last="Tang">Weiqing Tang</name><name sortKey="Wei, Guanghui" sort="Wei, Guanghui" uniqKey="Wei G" first="Guanghui" last="Wei">Guanghui Wei</name><name sortKey="Xiong, Geng" sort="Xiong, Geng" uniqKey="Xiong G" first="Geng" last="Xiong">Geng Xiong</name><name sortKey="Zhang, Deying" sort="Zhang, Deying" uniqKey="Zhang D" first="Deying" last="Zhang">Deying Zhang</name></country><country name="États-Unis"><noRegion><name sortKey="Xiong, Geng" sort="Xiong, Geng" uniqKey="Xiong G" first="Geng" last="Xiong">Geng Xiong</name></noRegion><name sortKey="Aloi, Joseph A" sort="Aloi, Joseph A" uniqKey="Aloi J" first="Joseph A." last="Aloi">Joseph A. Aloi</name><name sortKey="Atala, Antony" sort="Atala, Antony" uniqKey="Atala A" first="Antony" last="Atala">Antony Atala</name><name sortKey="Bleyer, Anthony J" sort="Bleyer, Anthony J" uniqKey="Bleyer A" first="Anthony J." last="Bleyer">Anthony J. Bleyer</name><name sortKey="Bleyer, Michael E" sort="Bleyer, Michael E" uniqKey="Bleyer M" first="Michael E." last="Bleyer">Michael E. Bleyer</name><name sortKey="Furdui, Cristina M" sort="Furdui, Cristina M" uniqKey="Furdui C" first="Cristina M." last="Furdui">Cristina M. Furdui</name><name sortKey="Ma, Jian Xing" sort="Ma, Jian Xing" uniqKey="Ma J" first="Jian-Xing" last="Ma">Jian-Xing Ma</name><name sortKey="Yu, Jie" sort="Yu, Jie" uniqKey="Yu J" first="Jie" last="Yu">Jie Yu</name><name sortKey="Zhang, Deying" sort="Zhang, Deying" uniqKey="Zhang D" first="Deying" last="Zhang">Deying Zhang</name><name sortKey="Zhang, Yuanyuan" sort="Zhang, Yuanyuan" uniqKey="Zhang Y" first="Yuanyuan" last="Zhang">Yuanyuan Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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