| First Author | Yuan Y | Year | 2015 |
| Journal | Lab Invest | Volume | 95 |
| Issue | 12 | Pages | 1374-86 |
| PubMed ID | 26414307 | Mgi Jnum | J:227711 |
| Mgi Id | MGI:5702518 | Doi | 10.1038/labinvest.2015.118 |
| Citation | Yuan Y, et al. (2015) The roles of oxidative stress, endoplasmic reticulum stress, and autophagy in aldosterone/mineralocorticoid receptor-induced podocyte injury. Lab Invest 95(12):1374-86 |
| abstractText | Podocytes play an important role in the pathogenesis and progression of glomerulosclerosis. Recent studies indicate that aldosterone/mineralocorticoid receptor (MR) is a major contributor of chronic kidney disease (CKD) progression. Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the glomerular filtration barrier and proteinuria. The present study investigated the mechanisms by which aldosterone/MR mediated podocyte injury, focusing on the involvement of oxidative stress, endoplasmic reticulum (ER) stress, and autophagy. We observed that aldosterone/MR induced ER stress and podocyte injury both in vivo and in vitro. Blockade of ER stress significantly reduced aldosterone/MR-induced podocyte injury. In addition, we found that ER stress-induced podocyte injury was mediated by CCAAT/enhancer-binding protein (C/EBP) homologous protein (Chop). Interestingly, autophagy was also enhanced by aldosterone/MR. Pharmacological inhibition of autophagy resulted in increased apoptosis. Inhibition of ER stress significantly reduced aldosterone/MR-induced autophagy. In addition, the activation of ER stress increased the formation of autophagy, which protected podocytes from apoptosis. Moreover, we observed that the addition of ROS scavenger, N-acetyl cystein (NAC), blocked both ER stress and autophagy by aldosterone/MR. Collectively, these results suggest that oxidant stress-mediated aldosterone/MR-induced podocyte injury via activating ER stress, which then triggers both Chop-dependent apoptosis and autophagy to cope with the injury. These findings may guide us to therapeutic strategies for glomerular diseases. |
