IHG-1 promotes mitochondrial biogenesis by stabilizing PGC-1α
Data(s) |
2011
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Resumo |
Increased expression of Induced-by-High-Glucose 1 (IHG-1) associates with tubulointerstitial fibrosis in diabetic nephropathy. IHG-1 amplifies TGF-ß1 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-1a (PGC-1a). Conversely, inhibition of IHG-1 expression decreased mitochondrial mass, downregulated mitochondrial proteins, and PGC-1a-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-1a 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-1a-dependent processes, potentially contributing to the pathogenesis of renal fibrosis. |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Hickey , F B , Corcoran , J B , Docherty , N G , Griffin , B , Bhreathnach , U , Furlong , F , Martin , F , Godson , C & Murphy , M 2011 , ' IHG-1 promotes mitochondrial biogenesis by stabilizing PGC-1α ' Journal of the American Society of Nephrology , vol 22 , no. 8 , pp. 1475-85 . DOI: 10.1681/ASN.2010111154 |
Tipo |
article |