PMID- 28216152
OWN - NLM
STAT- MEDLINE
DCOM- 20170704
LR  - 20211204
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 168
DP  - 2017 Apr
TI  - 1,25-Dihydroxyvitamin-D3 prevents the development of diabetic cardiomyopathy in 
      type 1 diabetic rats by enhancing autophagy via inhibiting the 
      beta-catenin/TCF4/GSK-3beta/mTOR pathway.
PG  - 71-90
LID - S0960-0760(17)30041-9 [pii]
LID - 10.1016/j.jsbmb.2017.02.007 [doi]
AB  - Diabetic cardiomyopathy (DCM) can increase the risk of heart failure and death in 
      diabetic patients. However, no effective approaches are available to prevent its 
      progression and development. Studies have shown that vitamin D is greatly 
      implicated in cardiac hypertrophy and fibrosis, and there is a high prevalence of 
      vitamin D deficiency in diabetic patients. In this study, we investigated whether 
      1,25-Dihydroxyvitamin-D3 (1,25D3) can improve DCM through a vitamin D receptor 
      (VDR)-dependent mechanism associated with autophagy and the beta-catenin/T-cell 
      factor/lymphoid enhancer factor (TCF4)/glycogen synthase kinase-3beta 
      (GSK-3beta)/mammalian target of rapamycin (mTOR) pathway. In this study, 
      streptozotocin (STZ)-induced type 1 diabetic rats were established and were 
      treated with 1,25D3 and/or chloroquine and/or VDR gene silencing for 8 weeks 
      before being sacrificed. Compared with untreated diabetic rats, 1,25D3 partly 
      attenuated the myocardial hypertrophy and interstitial fibrosis, improved cardiac 
      function and restored the impaired cardiac autophagy in diabetic rats, all of 
      which were reversed by silencing the VDR gene in diabetic rats. In high-glucose 
      cultured H9C2 cells, 1,25D3 increased autophagy in a dose-dependent manner. 
      Besides, the beta-catenin/TCF4/GSK-3beta and mTOR signaling were activated both in 
      diabetic rats and in high-glucose cultured H9C2 cells. Treatment with 1,25D3 
      inhibited the beta-catenin/TCF4/GSK-3beta and mTOR signaling in H9C2 cells, whereas 
      co-treatment with lithium chloride (LiCl) reversed this situation and abolished 
      the beneficial effect of 1,25D3 on autophagy. These data suggest that 1,25D3 may 
      improve DCM in type 1 diabetic rats by modulating autophagy through the 
      beta-catenin/TCF4/GSK-3beta and mTOR pathway. Vitamin D may exist as a new therapeutic 
      target for the treatment of DCM.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Wei, Huili
AU  - Wei H
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China. Electronic address: whl880410@163.com.
FAU - Qu, Hua
AU  - Qu H
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China. Electronic address: 276647689@qq.com.
FAU - Wang, Hang
AU  - Wang H
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China. Electronic address: 373776507@qq.com.
FAU - Ji, Baolan
AU  - Ji B
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China.
FAU - Ding, Yao
AU  - Ding Y
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China.
FAU - Liu, Dan
AU  - Liu D
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China.
FAU - Duan, Yang
AU  - Duan Y
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China.
FAU - Liang, Huimin
AU  - Liang H
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China.
FAU - Peng, Chuan
AU  - Peng C
AD  - Laboratory of Lipid and Glucose Metabolism, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400016, China.
FAU - Xiao, Xiaoqiu
AU  - Xiao X
AD  - Laboratory of Lipid and Glucose Metabolism, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400016, China.
FAU - Deng, Huacong
AU  - Deng H
AD  - Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical 
      University, No. 1 Youyi Road, Yuan Jiagang, Yuzhong District, Chongqing 400016, 
      China. Electronic address: denghuacong_111@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170217
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Ctnnb1 protein, rat)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Tcf4 protein, rat)
RN  - 0 (Transcription Factor 4)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - FXC9231JVH (Calcitriol)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
EIN - J Steroid Biochem Mol Biol. 2017 Nov;174:312-313. PMID: 29102300
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Blood Pressure
MH  - Calcitriol/*pharmacology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/metabolism
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Diabetes Mellitus, Type 1/metabolism
MH  - Diabetic Cardiomyopathies/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Echocardiography
MH  - Gene Silencing
MH  - Glucose/metabolism
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tissue Distribution
MH  - Transcription Factor 4
MH  - Transcription Factors/metabolism
MH  - beta Catenin/metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Diabetic cardiomyopathy
OT  - Type 1 diabetes
OT  - Vitamin D
EDAT- 2017/02/22 06:00
MHDA- 2017/07/05 06:00
CRDT- 2017/02/21 06:00
PHST- 2016/11/04 00:00 [received]
PHST- 2017/02/09 00:00 [revised]
PHST- 2017/02/09 00:00 [accepted]
PHST- 2017/02/22 06:00 [pubmed]
PHST- 2017/07/05 06:00 [medline]
PHST- 2017/02/21 06:00 [entrez]
AID - S0960-0760(17)30041-9 [pii]
AID - 10.1016/j.jsbmb.2017.02.007 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2017 Apr;168:71-90. doi: 10.1016/j.jsbmb.2017.02.007. 
      Epub 2017 Feb 17.