Protective effect of COMP-angiopoietin-1 on cyclosporine-induced renal injury in mice

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dc.contributor.authorLee, Sikko
dc.contributor.authorKim, Wonko
dc.contributor.authorKim, Duk Hoonko
dc.contributor.authorMoon, Sang-Okko
dc.contributor.authorJung, Yu Jinko
dc.contributor.authorLee, Ae Sinko
dc.contributor.authorKang, Kyung Pyoko
dc.contributor.authorJang, Kyu Yuriko
dc.contributor.authorLee, Sang Yongko
dc.contributor.authorSung, Mi Jeongko
dc.contributor.authorKoh, Gou Youngko
dc.contributor.authorPark, Sung Kwangko
dc.date.accessioned2013-03-08T10:39:27Z-
dc.date.available2013-03-08T10:39:27Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2008-
dc.identifier.citationNEPHROLOGY DIALYSIS TRANSPLANTATION, v.23, no.9, pp.2784 - 2794-
dc.identifier.issn0931-0509-
dc.identifier.urihttp://hdl.handle.net/10203/92852-
dc.description.abstractBackground. Peritubular capillary injury induces chronic hypoxia in the renal tubulointerstitium, and renal peritubular capillary dysfunction is an early event that contributes to tubulointerstitial fibrosis. Cyclosporine A (CsA) is a potent immunosuppressant and improves survival of renal allografts. However, the limitation of CsA use is chronic nephrotoxicity. A soluble, stable and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1 has been developed. We investigated whether COMP-Ang1 ameliorates CsA-induced renal injury. Methods. CsA-treated mice were injected with recombinant adenovirus expressing either COMP-Ang1 or LacZ. Histology, inflammatory, haemodynamic and fibrotic parameters, and signalling pathway were evaluated. Results. Histologic examination showed that COMP-Ang1 significantly decreased CsA-induced tubular damage and tubulointerstitial fibrosis. CsA-induced increases in macrophage infiltration and expression of MCP-1 and ICAM-1 after CsA treatment were significantly reduced by COMP-Ang1. Treatment with COMP-Ang1 also decreased the CsA-induced increases in TGF-beta 1 and Smad 2/3 levels while increasing Smad 7 levels. Laser-Doppler sonographic findings and endothelial factor VIII staining revealed that COMP-Ang1 preserved the integrity of peritubular vasculature and intrarenal haemodynamics from the CsA-induced renal injury. COMP-Ang1 inhibited tubular cell apoptosis while increasing tubular cell proliferation in CsA-induced renal injury. Conclusions. These results indicate that COMP-Ang1 exhibited a protective effect on damaged peritubular capillaries, haemodynamic alteration and inflammation in CsA-induced renal injury. Thus, COMP-Ang1 may be useful as a therapeutic and prophylactic agent for specific protection against endothelial dysfunction and inflammation.-
dc.languageEnglish-
dc.publisherOXFORD UNIV PRESS-
dc.subjectLEUKOCYTE ADHESION-
dc.subjectENDOTHELIAL-CELLS-
dc.subjectLONG-TERM-
dc.subjectAPOPTOSIS-
dc.subjectNEPHROTOXICITY-
dc.subjectCHEMOKINES-
dc.subjectEXPRESSION-
dc.subjectCOMP-ANG1-
dc.subjectDAMAGE-
dc.titleProtective effect of COMP-angiopoietin-1 on cyclosporine-induced renal injury in mice-
dc.typeArticle-
dc.identifier.wosid000259372400016-
dc.identifier.scopusid2-s2.0-58549084583-
dc.type.rimsART-
dc.citation.volume23-
dc.citation.issue9-
dc.citation.beginningpage2784-
dc.citation.endingpage2794-
dc.citation.publicationnameNEPHROLOGY DIALYSIS TRANSPLANTATION-
dc.identifier.doi10.1093/ndt/gfn168-
dc.contributor.localauthorKoh, Gou Young-
dc.contributor.nonIdAuthorLee, Sik-
dc.contributor.nonIdAuthorKim, Won-
dc.contributor.nonIdAuthorKim, Duk Hoon-
dc.contributor.nonIdAuthorMoon, Sang-Ok-
dc.contributor.nonIdAuthorJung, Yu Jin-
dc.contributor.nonIdAuthorLee, Ae Sin-
dc.contributor.nonIdAuthorKang, Kyung Pyo-
dc.contributor.nonIdAuthorJang, Kyu Yuri-
dc.contributor.nonIdAuthorLee, Sang Yong-
dc.contributor.nonIdAuthorSung, Mi Jeong-
dc.contributor.nonIdAuthorPark, Sung Kwang-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorCOMP-angiopoietin-1-
dc.subject.keywordAuthorcyclosporine A-
dc.subject.keywordAuthorendothelial cells-
dc.subject.keywordAuthorrenal fibrosis-
dc.subject.keywordPlusLEUKOCYTE ADHESION-
dc.subject.keywordPlusENDOTHELIAL-CELLS-
dc.subject.keywordPlusLONG-TERM-
dc.subject.keywordPlusAPOPTOSIS-
dc.subject.keywordPlusNEPHROTOXICITY-
dc.subject.keywordPlusCHEMOKINES-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusCOMP-ANG1-
dc.subject.keywordPlusDAMAGE-
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