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

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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 - Dec 10 2012

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Podocytes
Calcitriol Receptors
Diabetic Nephropathies
Vitamin D
Albuminuria
Transgenic Mice
Apoptosis
Kidney
Inbred DBA Mouse
Experimental Diabetes Mellitus
Transgenes
Fibrosis
Glucose
Wounds and Injuries

ASJC Scopus subject areas

  • Nephrology

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Vitamin D receptor signaling in podocytes protects against diabetic nephropathy. / Wang, Youli; Deb, Dilip K.; Zhang, Zhongyi; Sun, Tao; Liu, Weicheng; Yoon, Dosuk; Kong, Juan; Chen, Yunzi; Chang, Anthony; Li, Yan Chun.

In: Journal of the American Society of Nephrology, Vol. 23, No. 12, 10.12.2012, p. 1977-1986.

Research output: Contribution to journalArticle

Wang, Y, Deb, DK, Zhang, Z, Sun, T, Liu, W, Yoon, D, Kong, J, Chen, Y, Chang, A & Li, YC 2012, 'Vitamin D receptor signaling in podocytes protects against diabetic nephropathy', Journal of the American Society of Nephrology, vol. 23, no. 12, pp. 1977-1986. https://doi.org/10.1681/ASN.2012040383
Wang, Youli ; Deb, Dilip K. ; Zhang, Zhongyi ; Sun, Tao ; Liu, Weicheng ; Yoon, Dosuk ; Kong, Juan ; Chen, Yunzi ; Chang, Anthony ; Li, Yan Chun. / Vitamin D receptor signaling in podocytes protects against diabetic nephropathy. In: Journal of the American Society of Nephrology. 2012 ; Vol. 23, No. 12. pp. 1977-1986.
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