PMID- 23123403
OWN - NLM
STAT- MEDLINE
DCOM- 20130204
LR  - 20211021
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 23
IP  - 12
DP  - 2012 Dec
TI  - Vitamin D receptor signaling in podocytes protects against diabetic nephropathy.
PG  - 1977-86
LID - 10.1681/ASN.2012040383 [doi]
AB  - 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.
FAU - Wang, Youli
AU  - Wang Y
AD  - Department of Medicine, Division of Biological Sciences, The University of 
      Chicago, Chicago, IL 60637, USA.
FAU - Deb, Dilip K
AU  - Deb DK
FAU - Zhang, Zhongyi
AU  - Zhang Z
FAU - Sun, Tao
AU  - Sun T
FAU - Liu, Weicheng
AU  - Liu W
FAU - Yoon, Dosuk
AU  - Yoon D
FAU - Kong, Juan
AU  - Kong J
FAU - Chen, Yunzi
AU  - Chen Y
FAU - Chang, Anthony
AU  - Chang A
FAU - Li, Yan Chun
AU  - Li YC
LA  - eng
GR  - UL1 RR024999/RR/NCRR NIH HHS/United States
GR  - P30 CA014599/CA/NCI NIH HHS/United States
GR  - R01 HL085793/HL/NHLBI NIH HHS/United States
GR  - 5P30CA014599-36/CA/NCI NIH HHS/United States
GR  - UL1RR024999/RR/NCRR NIH HHS/United States
GR  - HL085793/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121102
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (NPHS2 protein)
RN  - 0 (Receptors, Calcitriol)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Diabetes Mellitus, Experimental/*complications/metabolism
MH  - Diabetic Nephropathies/genetics/*metabolism
MH  - Female
MH  - Humans
MH  - Hyperglycemia/*complications/metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Podocytes/*metabolism
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - Receptors, Calcitriol/*metabolism
PMC - PMC3507366
EDAT- 2012/11/06 06:00
MHDA- 2013/02/05 06:00
PMCR- 2013/11/30
CRDT- 2012/11/06 06:00
PHST- 2012/11/06 06:00 [entrez]
PHST- 2012/11/06 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
PHST- 2013/11/30 00:00 [pmc-release]
AID - ASN.2012040383 [pii]
AID - 2012040383 [pii]
AID - 10.1681/ASN.2012040383 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2012 Dec;23(12):1977-86. doi: 10.1681/ASN.2012040383. Epub 2012 
      Nov 2.