Vitamin D receptor signaling in podocytes protects against diabetic nephropathy

Youli Wang, Dilip K. Deb, Zhongyi Zhang, Tao Sun, Weicheng Liu, Dosuk Yoon, Juan Kong, Yunzi Chen, Anthony Chang, Yan Chun Li

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1977-1986
Number of pages10
JournalJournal of the American Society of Nephrology
Volume23
Issue number12
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Nephrology

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