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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Authors | Youli Wang, Dilip K Deb, Zhongyi Zhang, Tao Sun, Weicheng Liu, Dosuk Yoon, Juan Kong, Yunzi Chen, Anthony Chang, Yan Chun Li |
Journal | Journal of the American Society of Nephrology : JASN
(J Am Soc Nephrol)
Vol. 23
Issue 12
Pg. 1977-86
(Dec 2012)
ISSN: 1533-3450 [Electronic] United States |
PMID | 23123403
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins
- NPHS2 protein
- Receptors, Calcitriol
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Topics |
- Animals
- Apoptosis
- Diabetes Mellitus, Experimental
(complications, metabolism)
- Diabetic Nephropathies
(genetics, metabolism)
- Female
- Humans
- Hyperglycemia
(complications, metabolism)
- Intracellular Signaling Peptides and Proteins
(genetics)
- Male
- Membrane Proteins
(genetics)
- Mice
- Mice, Inbred DBA
- Mice, Knockout
- Podocytes
(metabolism)
- Pregnancy
- Promoter Regions, Genetic
- Receptors, Calcitriol
(metabolism)
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