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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A novel role of CCN3 in regulating endothelial inflammation</title><author><name sortKey="Lin, Zhiyong" sort="Lin, Zhiyong" uniqKey="Lin Z" first="Zhiyong" last="Lin">Zhiyong Lin</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Natesan, Viswanath" sort="Natesan, Viswanath" uniqKey="Natesan V" first="Viswanath" last="Natesan">Viswanath Natesan</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Shi, Hong" sort="Shi, Hong" uniqKey="Shi H" first="Hong" last="Shi">Hong Shi</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Hamik, Anne" sort="Hamik, Anne" uniqKey="Hamik A" first="Anne" last="Hamik">Anne Hamik</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Kawanami, Daiji" sort="Kawanami, Daiji" uniqKey="Kawanami D" first="Daiji" last="Kawanami">Daiji Kawanami</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Hao, Caili" sort="Hao, Caili" uniqKey="Hao C" first="Caili" last="Hao">Caili Hao</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Mahabaleshwar, Ganapati H" sort="Mahabaleshwar, Ganapati H" uniqKey="Mahabaleshwar G" first="Ganapati H." last="Mahabaleshwar">Ganapati H. Mahabaleshwar</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Weiye" sort="Wang, Weiye" uniqKey="Wang W" first="Weiye" last="Wang">Weiye Wang</name><affiliation><nlm:aff id="Aff2">Aab Cardiovascular Research Institute and Department of Medicine, Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY USA</nlm:aff></affiliation></author><author><name sortKey="Jin, Zheng Gen" sort="Jin, Zheng Gen" uniqKey="Jin Z" first="Zheng-Gen" last="Jin">Zheng-Gen Jin</name><affiliation><nlm:aff id="Aff2">Aab Cardiovascular Research Institute and Department of Medicine, Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY USA</nlm:aff></affiliation></author><author><name sortKey="Atkins, G Brandon" sort="Atkins, G Brandon" uniqKey="Atkins G" first="G. Brandon" last="Atkins">G. Brandon Atkins</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Firth, Sue M" sort="Firth, Sue M" uniqKey="Firth S" first="Sue M." last="Firth">Sue M. Firth</name><affiliation><nlm:aff id="Aff3">Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065 Australia</nlm:aff></affiliation></author><author><name sortKey="Rittie, Laure" sort="Rittie, Laure" uniqKey="Rittie L" first="Laure" last="Rittié">Laure Rittié</name><affiliation><nlm:aff id="Aff4">Department of Dermatology, University of Michigan, Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Perbal, Bernard" sort="Perbal, Bernard" uniqKey="Perbal B" first="Bernard" last="Perbal">Bernard Perbal</name><affiliation><nlm:aff id="Aff4">Department of Dermatology, University of Michigan, Ann Arbor, MI USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5">Laboratoire d’oncologie virale et moleculaire Université Paris, 7-D. Diderot, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="Aff6">L’Oreal R & D, Clark, NJ 07066 USA</nlm:aff></affiliation></author><author><name sortKey="Jain, Mukesh K" sort="Jain, Mukesh K" uniqKey="Jain M" first="Mukesh K." last="Jain">Mukesh K. Jain</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21063504</idno><idno type="pmc">2948121</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948121</idno><idno type="RBID">PMC:2948121</idno><idno type="doi">10.1007/s12079-010-0095-x</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000A02</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A02</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A novel role of CCN3 in regulating endothelial inflammation</title><author><name sortKey="Lin, Zhiyong" sort="Lin, Zhiyong" uniqKey="Lin Z" first="Zhiyong" last="Lin">Zhiyong Lin</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Natesan, Viswanath" sort="Natesan, Viswanath" uniqKey="Natesan V" first="Viswanath" last="Natesan">Viswanath Natesan</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Shi, Hong" sort="Shi, Hong" uniqKey="Shi H" first="Hong" last="Shi">Hong Shi</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Hamik, Anne" sort="Hamik, Anne" uniqKey="Hamik A" first="Anne" last="Hamik">Anne Hamik</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Kawanami, Daiji" sort="Kawanami, Daiji" uniqKey="Kawanami D" first="Daiji" last="Kawanami">Daiji Kawanami</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Hao, Caili" sort="Hao, Caili" uniqKey="Hao C" first="Caili" last="Hao">Caili Hao</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Mahabaleshwar, Ganapati H" sort="Mahabaleshwar, Ganapati H" uniqKey="Mahabaleshwar G" first="Ganapati H." last="Mahabaleshwar">Ganapati H. Mahabaleshwar</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Weiye" sort="Wang, Weiye" uniqKey="Wang W" first="Weiye" last="Wang">Weiye Wang</name><affiliation><nlm:aff id="Aff2">Aab Cardiovascular Research Institute and Department of Medicine, Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY USA</nlm:aff></affiliation></author><author><name sortKey="Jin, Zheng Gen" sort="Jin, Zheng Gen" uniqKey="Jin Z" first="Zheng-Gen" last="Jin">Zheng-Gen Jin</name><affiliation><nlm:aff id="Aff2">Aab Cardiovascular Research Institute and Department of Medicine, Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY USA</nlm:aff></affiliation></author><author><name sortKey="Atkins, G Brandon" sort="Atkins, G Brandon" uniqKey="Atkins G" first="G. Brandon" last="Atkins">G. Brandon Atkins</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author><author><name sortKey="Firth, Sue M" sort="Firth, Sue M" uniqKey="Firth S" first="Sue M." last="Firth">Sue M. Firth</name><affiliation><nlm:aff id="Aff3">Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065 Australia</nlm:aff></affiliation></author><author><name sortKey="Rittie, Laure" sort="Rittie, Laure" uniqKey="Rittie L" first="Laure" last="Rittié">Laure Rittié</name><affiliation><nlm:aff id="Aff4">Department of Dermatology, University of Michigan, Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Perbal, Bernard" sort="Perbal, Bernard" uniqKey="Perbal B" first="Bernard" last="Perbal">Bernard Perbal</name><affiliation><nlm:aff id="Aff4">Department of Dermatology, University of Michigan, Ann Arbor, MI USA</nlm:aff></affiliation><affiliation><nlm:aff id="Aff5">Laboratoire d’oncologie virale et moleculaire Université Paris, 7-D. Diderot, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="Aff6">L’Oreal R & D, Clark, NJ 07066 USA</nlm:aff></affiliation></author><author><name sortKey="Jain, Mukesh K" sort="Jain, Mukesh K" uniqKey="Jain M" first="Mukesh K." last="Jain">Mukesh K. Jain</name><affiliation><nlm:aff id="Aff1">University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Cell Communication and Signaling</title><idno type="ISSN">1873-9601</idno><idno type="eISSN">1873-961X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The vascular endothelium plays a fundamental role in the health and disease of the cardiovascular system. The molecular mechanisms regulating endothelial homeostasis, however, remain incompletely understood. CCN3, a member of the CCN (<italic>C</italic>yr61, <italic>C</italic>tgf, <italic>N</italic>ov) family of cell growth and differentiation regulators, has been shown to play an important role in numerous cell types. The function of CCN3 in endothelial cells has yet to be elucidated. Immunohistochemical analysis of CCN3 expression in mouse tissues revealed robust immunoreactivity in the endothelium of large arteries, small resistance vessels, and veins. We found that CCN3 expression in human umbilical vein endothelial cells (HUVECs) is transcriptionally induced by laminar shear stress (LSS) and HMG CoA-reductase inhibitors (statins). Promoter analyses identified the transcription factor Kruppel-like factor 2 (KLF2) as a direct regulator of CCN3 expression. In contrast to LSS, proinflammatory cytokines reduced CCN3 expression. Adenoviral overexpression of CCN3 in HUVEC markedly inhibited the cytokine-mediated induction of vascular adhesion molecule-1 (VCAM-1). Consistent with this observation, CCN3 significantly reduced monocyte adhesion. Conversely, CCN3 knockdown in HUVECs resulted in enhancement of cytokine-induced VCAM-1 expression. Concordant effects were observed on monocyte adhesion. Gain and loss-of-function mechanistic studies demonstrated that CCN3 negatively regulates nuclear factor kappaB (NF-κB) activity by reducing its translocation into the nucleus and subsequent binding to the VCAM-1 promoter, suggesting that CCN3’s anti-inflammatory effects occur secondary to inhibition of NF-κB nuclear accumulation. This study identifies CCN3 as a novel regulator of endothelial proinflammatory activation.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Cell Commun Signal</journal-id><journal-title-group><journal-title>Journal of Cell Communication and Signaling</journal-title></journal-title-group><issn pub-type="ppub">1873-9601</issn><issn pub-type="epub">1873-961X</issn><publisher><publisher-name>Springer Netherlands</publisher-name><publisher-loc>Dordrecht</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21063504</article-id><article-id pub-id-type="pmc">2948121</article-id><article-id pub-id-type="publisher-id">95</article-id><article-id pub-id-type="doi">10.1007/s12079-010-0095-x</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>A novel role of CCN3 in regulating endothelial inflammation</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Lin</surname><given-names>Zhiyong</given-names></name><address><phone>+1-216-3680767</phone><fax>+1-216-3680556</fax><email>zhiyong.lin@case.edu</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Natesan</surname><given-names>Viswanath</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hamik</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kawanami</surname><given-names>Daiji</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hao</surname><given-names>Caili</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mahabaleshwar</surname><given-names>Ganapati H.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Weiye</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Jin</surname><given-names>Zheng-Gen</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Atkins</surname><given-names>G. Brandon</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Firth</surname><given-names>Sue M.</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rittié</surname><given-names>Laure</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Perbal</surname><given-names>Bernard</given-names></name><xref ref-type="aff" rid="Aff4">4</xref><xref ref-type="aff" rid="Aff5">5</xref><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Jain</surname><given-names>Mukesh K.</given-names></name><address><phone>+1-216-3683607</phone><fax>+1-216-3680556</fax><email>mukesh.jain2@case.edu</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label>University Hospitals Harrington-McLaughlin Heart & Vascular Institute and Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, Wolstein Research Building, 2103 Cornell Road, Room 4-537, Cleveland, OH 44106-7290 USA</aff><aff id="Aff2"><label>2</label>Aab Cardiovascular Research Institute and Department of Medicine, Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY USA</aff><aff id="Aff3"><label>3</label>Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065 Australia</aff><aff id="Aff4"><label>4</label>Department of Dermatology, University of Michigan, Ann Arbor, MI USA</aff><aff id="Aff5"><label>5</label>Laboratoire d’oncologie virale et moleculaire Université Paris, 7-D. Diderot, Paris, France</aff><aff id="Aff6"><label>6</label>L’Oreal R & D, Clark, NJ 07066 USA</aff></contrib-group><pub-date pub-type="epub"><day>11</day><month>8</month><year>2010</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2010</year></pub-date><volume>4</volume><issue>3</issue><fpage>141</fpage><lpage>153</lpage><history><date date-type="received"><day>27</day><month>4</month><year>2010</year></date><date date-type="accepted"><day>22</day><month>7</month><year>2010</year></date></history><permissions><copyright-statement>© The International CCN Society 2010</copyright-statement></permissions><abstract><p>The vascular endothelium plays a fundamental role in the health and disease of the cardiovascular system. The molecular mechanisms regulating endothelial homeostasis, however, remain incompletely understood. CCN3, a member of the CCN (<italic>C</italic>yr61, <italic>C</italic>tgf, <italic>N</italic>ov) family of cell growth and differentiation regulators, has been shown to play an important role in numerous cell types. The function of CCN3 in endothelial cells has yet to be elucidated. Immunohistochemical analysis of CCN3 expression in mouse tissues revealed robust immunoreactivity in the endothelium of large arteries, small resistance vessels, and veins. We found that CCN3 expression in human umbilical vein endothelial cells (HUVECs) is transcriptionally induced by laminar shear stress (LSS) and HMG CoA-reductase inhibitors (statins). Promoter analyses identified the transcription factor Kruppel-like factor 2 (KLF2) as a direct regulator of CCN3 expression. In contrast to LSS, proinflammatory cytokines reduced CCN3 expression. Adenoviral overexpression of CCN3 in HUVEC markedly inhibited the cytokine-mediated induction of vascular adhesion molecule-1 (VCAM-1). Consistent with this observation, CCN3 significantly reduced monocyte adhesion. Conversely, CCN3 knockdown in HUVECs resulted in enhancement of cytokine-induced VCAM-1 expression. Concordant effects were observed on monocyte adhesion. Gain and loss-of-function mechanistic studies demonstrated that CCN3 negatively regulates nuclear factor kappaB (NF-κB) activity by reducing its translocation into the nucleus and subsequent binding to the VCAM-1 promoter, suggesting that CCN3’s anti-inflammatory effects occur secondary to inhibition of NF-κB nuclear accumulation. This study identifies CCN3 as a novel regulator of endothelial proinflammatory activation.</p></abstract><kwd-group><title>Keywords</title><kwd>CCN3</kwd><kwd>Endothelium</kwd><kwd>Inflammation</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The International CCN Society 2010</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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