PMID- 28069388
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20181113
IS  - 1096-0945 (Electronic)
IS  - 0014-4800 (Print)
IS  - 0014-4800 (Linking)
VI  - 102
IP  - 1
DP  - 2017 Feb
TI  - Vitamin D receptor deficit induces activation of renin angiotensin system via 
      SIRT1 modulation in podocytes.
PG  - 97-105
LID - S0014-4800(16)30444-0 [pii]
LID - 10.1016/j.yexmp.2017.01.001 [doi]
AB  - Vitamin D receptor (VDR) deficient status has been shown to be associated with 
      the activation of renin angiotensin system (RAS). We hypothesized that lack of 
      VDR would enhance p53 expression in podocytes through down regulation of SIRT1; 
      the former would enhance the transcription of angiotensinogen (Agt) and 
      angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal 
      tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, 
      and AT1R. In vitro studies, VDR knockout podocytes not only displayed up 
      regulation p53 but also displayed enhanced expression of Agt, renin and AT1R. VDR 
      deficient podocytes also displayed an increase in mRNA expression for p53, Agt, 
      renin, and AT1R. Interestingly, renal tissues of VDR-M as well as VDR 
      heterozygous (h) mice displayed attenuated expression of deacetylase SIRT1. Renal 
      tissues of VDR-M mice showed acetylation of p53 at lysine (K) 382 residues 
      inferring that enhanced p53 expression in renal tissues could be the result of 
      ongoing acetylation, a consequence of SIRT1 deficient state. Notably, podocytes 
      lacking SIRT1 not only showed acetylation of p53 at lysine (K) 382 residues but 
      also displayed enhanced p53 expression. Either silencing of SIRT1/VDR or 
      treatment with high glucose enhanced podocyte PPAR-y expression, whereas, 
      immunoprecipitation (IP) of their lysates with anti-retinoid X receptor (RXR) 
      antibody revealed presence of PPAR-y. It appears that either the deficit of SIRT1 
      has de-repressed expression of PPAR-y or enhanced podocyte expression of PPAR-y 
      (in the absence of VDR) has contributed to the down regulation of SIRT1.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Chandel, Nirupama
AU  - Chandel N
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA.
FAU - Ayasolla, Kamesh
AU  - Ayasolla K
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA.
FAU - Wen, Hongxiu
AU  - Wen H
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA.
FAU - Lan, Xiqian
AU  - Lan X
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA.
FAU - Haque, Shabirul
AU  - Haque S
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA.
FAU - Saleem, Moin A
AU  - Saleem MA
AD  - Renal Academic Unit, University of Bristol, UK.
FAU - Malhotra, Ashwani
AU  - Malhotra A
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA.
FAU - Singhal, Pravin C
AU  - Singhal PC
AD  - Department of Medicine, Hofstra Northwell Health Medical School and Feinstein 
      Institute for Medical Research, New York, USA. Electronic address: 
      psinghal@nshs.edu.
LA  - eng
GR  - R01 DK083931/DK/NIDDK NIH HHS/United States
GR  - R01 DK084910/DK/NIDDK NIH HHS/United States
GR  - R01 DK098074/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170106
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 11002-13-4 (Angiotensinogen)
RN  - EC 3.4.23.15 (Renin)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Acetylation
MH  - Angiotensinogen/genetics/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Humans
MH  - Kidney/cytology/metabolism
MH  - Lysine/genetics/metabolism
MH  - Mice, Knockout
MH  - Models, Genetic
MH  - Podocytes/cytology/*metabolism
MH  - RNA Interference
MH  - Receptor, Angiotensin, Type 1/genetics/metabolism
MH  - Receptors, Calcitriol/deficiency/*genetics
MH  - Renin/genetics/metabolism
MH  - Renin-Angiotensin System/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sirtuin 1/*genetics/metabolism
MH  - Tumor Suppressor Protein p53/genetics/metabolism
PMC - PMC5331620
MID - NIHMS844504
EDAT- 2017/01/11 06:00
MHDA- 2017/06/02 06:00
PMCR- 2018/02/01
CRDT- 2017/01/11 06:00
PHST- 2016/12/29 00:00 [received]
PHST- 2017/01/01 00:00 [accepted]
PHST- 2017/01/11 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
PHST- 2017/01/11 06:00 [entrez]
PHST- 2018/02/01 00:00 [pmc-release]
AID - S0014-4800(16)30444-0 [pii]
AID - 10.1016/j.yexmp.2017.01.001 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 2017 Feb;102(1):97-105. doi: 10.1016/j.yexmp.2017.01.001. Epub 
      2017 Jan 6.