PMID- 29180262
OWN - NLM
STAT- MEDLINE
DCOM- 20181023
LR  - 20181023
IS  - 1874-1754 (Electronic)
IS  - 0167-5273 (Linking)
VI  - 257
DP  - 2018 Apr 15
TI  - Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to 
      hypertension-induced cardiac hypertrophy.
PG  - 283-290
LID - S0167-5273(17)33565-9 [pii]
LID - 10.1016/j.ijcard.2017.10.102 [doi]
AB  - Cardiac hypertrophy is a major characteristic of early-stage hypertension-related 
      heart failure. We have found that the insulin-like growth factor receptor II 
      (IGF-IIR) signaling was critical for hypertensive angiotensin II-induced 
      cardiomyocyte hypertrophy and apoptosis. Moreover, this IGF-IIR signaling was 
      elegantly modulated by the heat shock transcription factors (HSFs) during heart 
      failure. However, the detailed mechanism by which HSFs regulates IGF-IIR during 
      hypertension-induced cardiac hypertrophy remains elusive. In this study, we found 
      that heat shock transcription factor 2 (HSF2) activated IGF-IIR to induce cardiac 
      hypertrophy for hypertension-induced heart failure. The transcriptional activity 
      of HSF2 appeared to be primarily mediated by SUMOylation via conjugation with 
      small ubiquitin-like modifier-1 (SUMO-1). The SUMOylation of HSF2 was severely 
      attenuated by MEL18 (also known as polycomb group ring finger 2 or PCGF2) in the 
      heart of spontaneously hypertensive rats (SHR). Inhibition of HSF2 SUMOylation 
      severely induced cardiac hypertrophy via IGF-IIR-mediated signaling in 
      hypertensive rats. Angiotensin II receptor type I blocker (ARB) treatment in 
      spontaneously hypertensive rats restored HSF2 SUMOylation and alleviated the 
      cardiac defects. Thus, our study uncovered a novel MEL18-SUMO-1-HSF2-IGF-IIR 
      pathway in the heart that profoundly influences cardiac hypertrophy for 
      hypertension-induced heart failure.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Huang, Chih-Yang
AU  - Huang CY
AD  - Translation Research Core, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan.
FAU - Kuo, Chia-Hua
AU  - Kuo CH
AD  - Department of Sports Sciences, University of Taipei, Taipei, Taiwan.
FAU - Pai, Pei-Ying
AU  - Pai PY
AD  - Division of Cardiology, China Medical University Hospital, Taichung, Taiwan.
FAU - Ho, Tsung-Jung
AU  - Ho TJ
AD  - School of Chinese Medicine, China Medical University, Taichung, Taiwan; Chinese 
      Medicine Department, China Medical University Beigang Hospital, Taiwan.
FAU - Lin, Yueh-Min
AU  - Lin YM
AD  - Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan; 
      Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and 
      Management, Miaoli, Taiwan.
FAU - Chen, Ray-Jade
AU  - Chen RJ
AD  - Department of Surgery, School of Medicine, College of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Tsai, Fuu-Jen
AU  - Tsai FJ
AD  - School of Chinese Medicine, China Medical University, Taichung, Taiwan.
FAU - Vijaya Padma, V
AU  - Vijaya Padma V
AD  - Department of Biotechnology, Bharathiar University, Coimbatore 641 046, India.
FAU - Kuo, Wei-Wen
AU  - Kuo WW
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, Taiwan.
FAU - Huang, Chih-Yang
AU  - Huang CY
AD  - School of Chinese Medicine, China Medical University, Taichung, Taiwan; Graduate 
      Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; 
      Department of Health and Nutrition Biotechnology, Asia University, Taichung, 
      Taiwan. Electronic address: cyhuang@mail.cmu.edu.tw.
LA  - eng
PT  - Journal Article
DEP - 20171110
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hsf2 protein, rat)
RN  - 0 (PCGF2 protein, human)
RN  - 0 (Receptor, IGF Type 2)
RN  - 0 (Transcription Factors)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
SB  - IM
MH  - Angiotensin II/pharmacology/toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Cardiomegaly/chemically induced/*metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - HEK293 Cells
MH  - Heat-Shock Proteins/antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Hypertension/chemically induced/*metabolism
MH  - Polycomb Repressive Complex 1/*metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Rats, Sprague-Dawley
MH  - Receptor, IGF Type 2/*biosynthesis
MH  - Sumoylation/drug effects/*physiology
MH  - Transcription Factors/antagonists & inhibitors/*metabolism
MH  - Up-Regulation/drug effects/physiology
OTO - NOTNLM
OT  - ANGII
OT  - HSF2
OT  - Hypertension
OT  - IGF-IIR
OT  - MEL18
OT  - SUMOylation
EDAT- 2017/11/29 06:00
MHDA- 2018/10/24 06:00
CRDT- 2017/11/29 06:00
PHST- 2017/07/28 00:00 [received]
PHST- 2017/10/16 00:00 [revised]
PHST- 2017/10/26 00:00 [accepted]
PHST- 2017/11/29 06:00 [pubmed]
PHST- 2018/10/24 06:00 [medline]
PHST- 2017/11/29 06:00 [entrez]
AID - S0167-5273(17)33565-9 [pii]
AID - 10.1016/j.ijcard.2017.10.102 [doi]
PST - ppublish
SO  - Int J Cardiol. 2018 Apr 15;257:283-290. doi: 10.1016/j.ijcard.2017.10.102. Epub 
      2017 Nov 10.