The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis
Identifieur interne : 001D58 ( Ncbi/Merge ); précédent : 001D57; suivant : 001D59The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis
Auteurs : Long Shuang Huang ; Biji Mathew ; Haiquan Li ; Yutong Zhao ; Shwu-Fan Ma ; Imre Noth ; Sekhar P. Reddy ; Anantha Harijith ; Peter V. Usatyuk ; Evgeny V. Berdyshev ; Naftali Kaminski ; Tong Zhou ; Wei Zhang ; Yanmin Zhang ; Jalees Rehman ; Sainath R. Kotha ; Travis O. Gurney ; Narasimham L. Parinandi ; Yves A. Lussier ; Joe G. N. Garcia ; Viswanathan NatarajanSource :
- American Journal of Respiratory and Critical Care Medicine [ 1073-449X ] ; 2014.
Abstract
Url:
DOI: 10.1164/rccm.201310-1917OC
PubMed: 24779708
PubMed Central: 4098083
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Reddy</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Harijith, Anantha" sort="Harijith, Anantha" uniqKey="Harijith A" first="Anantha" last="Harijith">Anantha Harijith</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Usatyuk, Peter V" sort="Usatyuk, Peter V" uniqKey="Usatyuk P" first="Peter V." last="Usatyuk">Peter V. Usatyuk</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Berdyshev, Evgeny V" sort="Berdyshev, Evgeny V" uniqKey="Berdyshev E" first="Evgeny V." last="Berdyshev">Evgeny V. Berdyshev</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Kaminski, Naftali" sort="Kaminski, Naftali" uniqKey="Kaminski N" first="Naftali" last="Kaminski">Naftali Kaminski</name><affiliation><nlm:aff id="aff6"></nlm:aff></affiliation></author><author><name sortKey="Zhou, Tong" sort="Zhou, Tong" uniqKey="Zhou T" first="Tong" last="Zhou">Tong Zhou</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Yanmin" sort="Zhang, Yanmin" uniqKey="Zhang Y" first="Yanmin" last="Zhang">Yanmin Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Rehman, Jalees" sort="Rehman, Jalees" uniqKey="Rehman J" first="Jalees" last="Rehman">Jalees Rehman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kotha, Sainath R" sort="Kotha, Sainath R" uniqKey="Kotha S" first="Sainath R." last="Kotha">Sainath R. Kotha</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Gurney, Travis O" sort="Gurney, Travis O" uniqKey="Gurney T" first="Travis O." last="Gurney">Travis O. Gurney</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Parinandi, Narasimham L" sort="Parinandi, Narasimham L" uniqKey="Parinandi N" first="Narasimham L." last="Parinandi">Narasimham L. Parinandi</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Lussier, Yves A" sort="Lussier, Yves A" uniqKey="Lussier Y" first="Yves A." last="Lussier">Yves A. Lussier</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Garcia, Joe G N" sort="Garcia, Joe G N" uniqKey="Garcia J" first="Joe G. N." last="Garcia">Joe G. N. Garcia</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Natarajan, Viswanathan" sort="Natarajan, Viswanathan" uniqKey="Natarajan V" first="Viswanathan" last="Natarajan">Viswanathan Natarajan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24779708</idno><idno type="pmc">4098083</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098083</idno><idno type="RBID">PMC:4098083</idno><idno type="doi">10.1164/rccm.201310-1917OC</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000866</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000866</idno><idno type="wicri:Area/Pmc/Curation">000842</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000842</idno><idno type="wicri:Area/Pmc/Checkpoint">000351</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000351</idno><idno type="wicri:Area/Ncbi/Merge">001D58</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis</title><author><name sortKey="Huang, Long Shuang" sort="Huang, Long Shuang" uniqKey="Huang L" first="Long Shuang" last="Huang">Long Shuang Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Mathew, Biji" sort="Mathew, Biji" uniqKey="Mathew B" first="Biji" last="Mathew">Biji Mathew</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Li, Haiquan" sort="Li, Haiquan" uniqKey="Li H" first="Haiquan" last="Li">Haiquan Li</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Zhao, Yutong" sort="Zhao, Yutong" uniqKey="Zhao Y" first="Yutong" last="Zhao">Yutong Zhao</name><affiliation><nlm:aff id="aff6"></nlm:aff></affiliation></author><author><name sortKey="Ma, Shwu Fan" sort="Ma, Shwu Fan" uniqKey="Ma S" first="Shwu-Fan" last="Ma">Shwu-Fan Ma</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Noth, Imre" sort="Noth, Imre" uniqKey="Noth I" first="Imre" last="Noth">Imre Noth</name><affiliation><nlm:aff id="aff7"></nlm:aff></affiliation></author><author><name sortKey="Reddy, Sekhar P" sort="Reddy, Sekhar P" uniqKey="Reddy S" first="Sekhar P." last="Reddy">Sekhar P. Reddy</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Harijith, Anantha" sort="Harijith, Anantha" uniqKey="Harijith A" first="Anantha" last="Harijith">Anantha Harijith</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Usatyuk, Peter V" sort="Usatyuk, Peter V" uniqKey="Usatyuk P" first="Peter V." last="Usatyuk">Peter V. Usatyuk</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Berdyshev, Evgeny V" sort="Berdyshev, Evgeny V" uniqKey="Berdyshev E" first="Evgeny V." last="Berdyshev">Evgeny V. Berdyshev</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Kaminski, Naftali" sort="Kaminski, Naftali" uniqKey="Kaminski N" first="Naftali" last="Kaminski">Naftali Kaminski</name><affiliation><nlm:aff id="aff6"></nlm:aff></affiliation></author><author><name sortKey="Zhou, Tong" sort="Zhou, Tong" uniqKey="Zhou T" first="Tong" last="Zhou">Tong Zhou</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Yanmin" sort="Zhang, Yanmin" uniqKey="Zhang Y" first="Yanmin" last="Zhang">Yanmin Zhang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Rehman, Jalees" sort="Rehman, Jalees" uniqKey="Rehman J" first="Jalees" last="Rehman">Jalees Rehman</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kotha, Sainath R" sort="Kotha, Sainath R" uniqKey="Kotha S" first="Sainath R." last="Kotha">Sainath R. Kotha</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Gurney, Travis O" sort="Gurney, Travis O" uniqKey="Gurney T" first="Travis O." last="Gurney">Travis O. Gurney</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Parinandi, Narasimham L" sort="Parinandi, Narasimham L" uniqKey="Parinandi N" first="Narasimham L." last="Parinandi">Narasimham L. Parinandi</name><affiliation><nlm:aff id="aff8"></nlm:aff></affiliation></author><author><name sortKey="Lussier, Yves A" sort="Lussier, Yves A" uniqKey="Lussier Y" first="Yves A." last="Lussier">Yves A. Lussier</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation><affiliation><nlm:aff id="aff5"></nlm:aff></affiliation></author><author><name sortKey="Garcia, Joe G N" sort="Garcia, Joe G N" uniqKey="Garcia J" first="Joe G. N." last="Garcia">Joe G. N. Garcia</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Natarajan, Viswanathan" sort="Natarajan, Viswanathan" uniqKey="Natarajan V" first="Viswanathan" last="Natarajan">Viswanathan Natarajan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author></analytic><series><title level="j">American Journal of Respiratory and Critical Care Medicine</title><idno type="ISSN">1073-449X</idno><idno type="eISSN">1535-4970</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Rationale:</bold> Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis.</p><p><bold>Objectives:</bold> To define a role for LYCAT in human and murine models of pulmonary fibrosis.</p><p><bold>Methods:</bold> We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge.</p><p><bold>Measurements and Main Results:</bold> LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. <italic>LYCAT</italic> mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, <italic>hLYCAT</italic> overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. <italic>In vitro</italic> studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection.</p><p><bold>Conclusions:</bold> This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis.</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">Am J Respir Crit Care Med</journal-id><journal-id journal-id-type="iso-abbrev">Am. J. Respir. Crit. Care Med</journal-id><journal-id journal-id-type="publisher-id">ajrccm</journal-id><journal-title-group><journal-title>American Journal of Respiratory and Critical Care Medicine</journal-title></journal-title-group><issn pub-type="ppub">1073-449X</issn><issn pub-type="epub">1535-4970</issn><publisher><publisher-name>American Thoracic Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24779708</article-id><article-id pub-id-type="pmc">4098083</article-id><article-id pub-id-type="publisher-manuscript">201310-1917OC</article-id><article-id pub-id-type="doi">10.1164/rccm.201310-1917OC</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject><subj-group><subject>Interstitial Lung Disease</subject></subj-group></subj-group></article-categories><title-group><article-title>The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Long Shuang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Mathew</surname><given-names>Biji</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Li</surname><given-names>Haiquan</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Yutong</given-names></name><xref ref-type="aff" rid="aff6"><sup>4</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Ma</surname><given-names>Shwu-Fan</given-names></name><xref ref-type="aff" rid="aff7"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Noth</surname><given-names>Imre</given-names></name><xref ref-type="aff" rid="aff7"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reddy</surname><given-names>Sekhar P.</given-names></name><xref ref-type="aff" rid="aff4"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Harijith</surname><given-names>Anantha</given-names></name><xref ref-type="aff" rid="aff4"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Usatyuk</surname><given-names>Peter V.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Berdyshev</surname><given-names>Evgeny V.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kaminski</surname><given-names>Naftali</given-names></name><xref ref-type="aff" rid="aff6"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Tong</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff4"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Yanmin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rehman</surname><given-names>Jalees</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kotha</surname><given-names>Sainath R.</given-names></name><xref ref-type="aff" rid="aff8"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gurney</surname><given-names>Travis O.</given-names></name><xref ref-type="aff" rid="aff8"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Parinandi</surname><given-names>Narasimham L.</given-names></name><xref ref-type="aff" rid="aff8"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lussier</surname><given-names>Yves A.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff5"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Garcia</surname><given-names>Joe G. N.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="author-notes" rid="fn2"><sup>†</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Natarajan</surname><given-names>Viswanathan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="author-notes" rid="fn2"><sup>†</sup></xref></contrib><aff id="aff1"><label><sup>1</sup></label>Department of Pharmacology</aff><aff id="aff2"><label><sup>2</sup></label>The Institute for Personalized Respiratory Medicine</aff><aff id="aff3"><label><sup>3</sup></label>Department of Medicine</aff><aff id="aff4"><label><sup>6</sup></label>Department of Pediatrics, and</aff><aff id="aff5"><label><sup>8</sup></label>Department of Engineering, The University of Illinois, Chicago, Illinois</aff><aff id="aff6"><label><sup>4</sup></label>Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania</aff><aff id="aff7"><label><sup>5</sup></label>Department of Medicine, University of Chicago, Chicago, Illinois; and</aff><aff id="aff8"><label><sup>7</sup></label>Davis Heart & Lung Research Institute and Division of Pulmonary and Critical Care Medicine, The Ohio State University, Columbus, Ohio</aff></contrib-group><author-notes><fn id="fn1"><label>*</label><p>These authors contributed equally to this work.</p></fn><fn id="fn2"><label><sup>†</sup></label><p>These authors contributed equally as senior authors to this work.</p></fn><corresp>Correspondence and requests for reprints should be addressed to Viswanathan Natarajan, Ph.D., Institute for Personalized Respiratory Medicine, COMRB, Room # 3137, 909 South Wolcott Avenue, Chicago, IL 60612. E-mail: <email xlink:href="visnatar@uic.edu">visnatar@uic.edu</email></corresp></author-notes><pub-date pub-type="epub-ppub"><day>1</day><month>6</month><year>2014</year><pmc-comment>string-date: June 1, 2014</pmc-comment>
</pub-date><pmc-comment>Fake epub and ppub dates generated by PMC from publisher
pub-date/@pub-type='epub-ppub' </pmc-comment>
<pub-date pub-type="epub"><day>1</day><month>6</month><year>2014</year><pmc-comment>string-date: June 1, 2014</pmc-comment>
</pub-date><pub-date pub-type="ppub"><day>1</day><month>6</month><year>2014</year><pmc-comment>string-date: June 1, 2014</pmc-comment>
</pub-date><volume>189</volume><issue>11</issue><fpage>1402</fpage><lpage>1415</lpage><history><date date-type="received"><day>29</day><month>10</month><year>2013</year></date><date date-type="accepted"><day>23</day><month>4</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 by the American Thoracic Society</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri content-type="pdf" xlink:href="rccm.201310-1917OC.pdf"></self-uri><abstract><p><bold>Rationale:</bold> Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis.</p><p><bold>Objectives:</bold> To define a role for LYCAT in human and murine models of pulmonary fibrosis.</p><p><bold>Methods:</bold> We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge.</p><p><bold>Measurements and Main Results:</bold> LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. <italic>LYCAT</italic> mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, <italic>hLYCAT</italic> overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. <italic>In vitro</italic> studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection.</p><p><bold>Conclusions:</bold> This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis.</p></abstract><kwd-group><title>Keywords</title><kwd>LYCAT</kwd><kwd>mitochondrial cardiolipin remodeling</kwd><kwd>bleomycin</kwd><kwd>IPF</kwd><kwd>apoptosis</kwd></kwd-group><counts><fig-count count="9"></fig-count><table-count count="0"></table-count><page-count count="14"></page-count></counts></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Berdyshev, Evgeny V" sort="Berdyshev, Evgeny V" uniqKey="Berdyshev E" first="Evgeny V." last="Berdyshev">Evgeny V. Berdyshev</name><name sortKey="Garcia, Joe G N" sort="Garcia, Joe G N" uniqKey="Garcia J" first="Joe G. N." last="Garcia">Joe G. N. Garcia</name><name sortKey="Gurney, Travis O" sort="Gurney, Travis O" uniqKey="Gurney T" first="Travis O." last="Gurney">Travis O. Gurney</name><name sortKey="Harijith, Anantha" sort="Harijith, Anantha" uniqKey="Harijith A" first="Anantha" last="Harijith">Anantha Harijith</name><name sortKey="Huang, Long Shuang" sort="Huang, Long Shuang" uniqKey="Huang L" first="Long Shuang" last="Huang">Long Shuang Huang</name><name sortKey="Kaminski, Naftali" sort="Kaminski, Naftali" uniqKey="Kaminski N" first="Naftali" last="Kaminski">Naftali Kaminski</name><name sortKey="Kotha, Sainath R" sort="Kotha, Sainath R" uniqKey="Kotha S" first="Sainath R." last="Kotha">Sainath R. Kotha</name><name sortKey="Li, Haiquan" sort="Li, Haiquan" uniqKey="Li H" first="Haiquan" last="Li">Haiquan Li</name><name sortKey="Lussier, Yves A" sort="Lussier, Yves A" uniqKey="Lussier Y" first="Yves A." last="Lussier">Yves A. Lussier</name><name sortKey="Ma, Shwu Fan" sort="Ma, Shwu Fan" uniqKey="Ma S" first="Shwu-Fan" last="Ma">Shwu-Fan Ma</name><name sortKey="Mathew, Biji" sort="Mathew, Biji" uniqKey="Mathew B" first="Biji" last="Mathew">Biji Mathew</name><name sortKey="Natarajan, Viswanathan" sort="Natarajan, Viswanathan" uniqKey="Natarajan V" first="Viswanathan" last="Natarajan">Viswanathan Natarajan</name><name sortKey="Noth, Imre" sort="Noth, Imre" uniqKey="Noth I" first="Imre" last="Noth">Imre Noth</name><name sortKey="Parinandi, Narasimham L" sort="Parinandi, Narasimham L" uniqKey="Parinandi N" first="Narasimham L." last="Parinandi">Narasimham L. Parinandi</name><name sortKey="Reddy, Sekhar P" sort="Reddy, Sekhar P" uniqKey="Reddy S" first="Sekhar P." last="Reddy">Sekhar P. Reddy</name><name sortKey="Rehman, Jalees" sort="Rehman, Jalees" uniqKey="Rehman J" first="Jalees" last="Rehman">Jalees Rehman</name><name sortKey="Usatyuk, Peter V" sort="Usatyuk, Peter V" uniqKey="Usatyuk P" first="Peter V." last="Usatyuk">Peter V. Usatyuk</name><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name><name sortKey="Zhang, Yanmin" sort="Zhang, Yanmin" uniqKey="Zhang Y" first="Yanmin" last="Zhang">Yanmin Zhang</name><name sortKey="Zhao, Yutong" sort="Zhao, Yutong" uniqKey="Zhao Y" first="Yutong" last="Zhao">Yutong Zhao</name><name sortKey="Zhou, Tong" sort="Zhou, Tong" uniqKey="Zhou T" first="Tong" last="Zhou">Tong Zhou</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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