1. Academic Validation
  2. Vitamin D receptor signaling in podocytes protects against diabetic nephropathy

Vitamin D receptor signaling in podocytes protects against diabetic nephropathy

  • J Am Soc Nephrol. 2012 Dec;23(12):1977-86. doi: 10.1681/ASN.2012040383.
Youli Wang 1 Dilip K Deb Zhongyi Zhang Tao Sun Weicheng Liu Dosuk Yoon Juan Kong Yunzi Chen Anthony Chang Yan Chun Li
Affiliations

Affiliation

  • 1 Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, IL 60637, USA.
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.

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