| First Author | Yuan Y | Year | 2012 |
| Journal | Kidney Int | Volume | 82 |
| Issue | 7 | Pages | 771-89 |
| PubMed ID | 22648295 | Mgi Jnum | J:198172 |
| Mgi Id | MGI:5495616 | Doi | 10.1038/ki.2012.188 |
| Citation | Yuan Y, et al. (2012) Activation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury. Kidney Int 82(7):771-89 |
| abstractText | Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), affects podocyte damage. Aldosterone-induced injury decreased PGC-1alpha expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1alpha by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1alpha, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1alpha at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1alpha may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1alpha expression and, consequently, podocyte integrity. |
