| First Author | Cheng H | Year | 2011 |
| Journal | J Am Soc Nephrol | Volume | 22 |
| Issue | 7 | Pages | 1240-51 |
| PubMed ID | 21737546 | Mgi Jnum | J:179350 |
| Mgi Id | MGI:5301834 | Doi | 10.1681/ASN.2010111149 |
| Citation | Cheng H, et al. (2011) Podocyte COX-2 exacerbates diabetic nephropathy by increasing podocyte (pro)renin receptor expression. J Am Soc Nephrol 22(7):1240-51 |
| abstractText | Diabetic nephropathy (DN) increases podocyte cyclooxygenase-2 (COX-2) expression, and COX-2 inhibition reduces proteinuria and glomerular injury in animal models of diabetes. To investigate the role of podocyte COX-2 in development of diabetic nephropathy, we employed a streptozotocin model of diabetic mellitus in wild-type and transgenic mice expressing COX-2 selectively in podocytes. Progressive albuminuria developed only in diabetic COX-2 transgenic mice despite hyperglycemia, BP, and GFR being similar to those in wild-type mice. Transgenic mice also manifested significant foot-process effacement, moderate mesangial expansion, and segmental thickening of the glomerular basement membrane. In cultured podocytes overexpressing COX-2, high glucose induced cell injury and increased both expression of the pro(renin) receptor and activation of the renin-angiotensin system. Downregulation of the (pro)renin receptor attenuated the injury induced by high glucose. In vivo, podocyte pro(renin) receptor expression increased in diabetic COX-2-transgenic mice, and treatment with a COX-2 inhibitor abrogated the upregulation of (pro)renin receptor and reduced albuminuria, foot-process effacement, and mesangial matrix expansion. In summary, these results demonstrate that increased expression of podocyte COX-2 predisposes to diabetic glomerular injury and that the (pro)renin receptor may be one mediator for this increased susceptibility to injury. |
