| First Author | Zhao M | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 11 | Pages | 12150-62 |
| PubMed ID | 26943584 | Mgi Jnum | J:315554 |
| Mgi Id | MGI:6829232 | Doi | 10.18632/oncotarget.7859 |
| Citation | Zhao M, et al. (2016) PGC-1alpha overexpression protects against aldosterone-induced podocyte depletion: role of mitochondria. Oncotarget 7(11):12150-62 |
| abstractText | Growing evidence has shown that podocyte number is a critical determinant for the development of glomerulosclerosis and progressive renal failure. We previously reported that mitochondrial dysfunction (MtD) is an early event in podocyte injury. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is an important modulator of mitochondrial biogenesis. Here, we investigated the role of PGC-1alpha overexpression in podocyte depletion and the involvement of mitochondria in this process. Following chronic aldosterone (Aldo) infusion for 14 days, we observed a remarkable podocyte loss, podocyte phenotypic changes, and albuminuria in WT mice. However, all these abnormalities were significantly attenuated in PGC-1alpha transgenic mice. Next, we examined mitochondrial function in both genotypes with or without Aldo infusion. As expected, Aldo-induced MtD in glomeruli was markedly improved in PGC-1alpha transgenic mice. In vitro, Aldo induced podocyte detachment and phenotypic changes in line with MtD in dose- and time-dependent manners. Similarly, ethidium bromide, an inducer of MtD, mimicked Aldo effects on podocyte detachment and phenotypic alterations. Notably, overexpression of PGC-1alpha in podocytes entirely reversed Aldo-induced podocyte detachment, phenotypic changes, and MtD. Taken together, these findings demonstrate that PGC-1alpha protects against podocyte depletion and phenotypic changes possibly by maintaining normal mitochondrial function. |
