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dc.contributor.authorHICKEY, FIONNUALA
dc.date.accessioned2014-11-24T14:19:54Z
dc.date.available2014-11-24T14:19:54Z
dc.date.issued2011
dc.date.submitted2011en
dc.identifier.citationHickey FB, Corcoran JB, Docherty NG, Griffin B, Bhreathnach U, Furlong F, Martin F, Godosn C, Murphy M, IHG-1 promotes mitochondrial biogenesis by stabilising PGC-1α, Journal of the American Society of Nephrology, 22, 8, 2011, 1475 - 1485en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/72142
dc.descriptionPUBLISHEDen
dc.description.abstractIncreased expression of Induced-by-High-Glucose 1 (IHG-1) associates with tubulointerstitial fibrosis in diabetic nephropathy. IHG-1 amplifies TGF-?1 signaling, but the functions of this highly-conserved protein are not well understood. IHG-1 contains a putative mitochondrial-localization domain, and here we report that IHG-1 is specifically localized to mitochondria. IHG-1 overexpression increased mitochondrial mass and stabilized peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?). Conversely, inhibition of IHG-1 expression decreased mitochondrial mass, downregulated mitochondrial proteins, and PGC-1?-regulated transcription factors, including nuclear respiratory factor 1 and mitochondrial transcription factor A (TFAM), and reduced activity of the TFAM promoter. In the unilateral ureteral obstruction model, we observed higher PGC-1? protein expression and IHG-1 levels with fibrosis. In a gene-expression database, we noted that renal biopsies of human diabetic nephropathy demonstrated higher expression of genes encoding key mitochondrial proteins, including cytochrome c and manganese superoxide dismutase, compared with control biopsies. In summary, these data suggest that IHG-1 increases mitochondrial biogenesis by promoting PGC-1?-dependent processes, potentially contributing to the pathogenesis of renal fibrosis.en
dc.description.sponsorshipThis work was funded by Science Foundation Ireland, the Health Research Board, and the Government of Ireland Programme for Research in Third Level Institutions.en
dc.format.extent1475en
dc.format.extent1485en
dc.language.isoenen
dc.relation.ispartofseriesJournal of the American Society of Nephrology;
dc.relation.ispartofseries22;
dc.relation.ispartofseries8;
dc.rightsYen
dc.subjectrenal fibrosisen
dc.titleIHG-1 Promotes Mitochondrial Biogenesis by Stabilizing PGC-1αen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/hickeyfb
dc.identifier.rssinternalid88624
dc.rights.ecaccessrightsOpenAccess
dc.identifier.rssurihttp://jasn.asnjournals.org/content/22/8/1475.longen


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