title: Vitamin D receptor signaling in podocytes protects against diabetic nephropathy.
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.
authors.affiliation: Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Youli
authors.initials: Y
authors.lastname: Wang
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Deb
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Weicheng
authors.initials: W
authors.lastname: Liu
authors.forename: Dosuk
authors.initials: D
authors.lastname: Yoon
authors.forename: Juan
authors.initials: J
authors.lastname: Kong
authors.forename: Yunzi
authors.initials: Y
authors.lastname: Chen
authors.forename: Anthony
authors.initials: A
authors.lastname: Chang
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D050199:Podocytes / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D018167:Receptors, Calcitriol