| First Author | Wang Y | Year | 2012 |
| Journal | J Am Soc Nephrol | Volume | 23 |
| Issue | 12 | Pages | 1977-86 |
| PubMed ID | 23123403 | Mgi Jnum | J:323181 |
| Mgi Id | MGI:6843429 | Doi | 10.1681/ASN.2012040383 |
| Citation | Wang Y, et al. (2012) Vitamin D receptor signaling in podocytes protects against diabetic nephropathy. J Am Soc Nephrol 23(12):1977-86 |
| abstractText | Vitamin D and its analogs have antiproteinuric activity and podocytes express the vitamin D receptor, but whether vitamin D signaling in podocytes accounts for this renoprotection is unknown. To investigate this question, we used the 2.5 kb podocin promoter to target Flag-tagged human vitamin D receptor (hVDR) to podocytes in DBA/2J mice. After the induction of diabetes with streptozotocin, transgenic mice had less albuminuria than wild-type controls. In transgenic mice, a low dose of the vitamin D analog doxercalciferol prevented albuminuria, markedly attenuated podocyte loss and apoptosis, and reduced glomerular fibrosis, but it had little effect on the progression of diabetic nephropathy in wild-type mice. Moreover, reconstitution of VDR-null mice with the hVDR transgene in podocytes rescued VDR-null mice from severe diabetes-related renal damage. In culture, 1,25-dihydroxyvitamin D suppressed high-glucose-induced apoptosis of podocytes by blocking p38- and ERK-mediated proapoptotic pathways. Taken together, these data provide strong evidence that vitamin D/VDR signaling in podocytes plays a critical role in the protection of the kidney from diabetic injury. |
