Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy

Chih Yang Huang, Chia Hua Kuo, Pei Ying Pai, Tsung Jung Ho, Yueh Min Lin, Ray Jade Chen, Fuu Jen Tsai, V. Vijaya Padma, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)283-290
JournalInternational Journal of Cardiology
Volume257
DOIs
Publication statusPublished - Apr 15 2018

Fingerprint

Sumoylation
Cardiomegaly
Up-Regulation
Hypertension
Heart Failure
Insulin-Like Growth Factor II
Inbred SHR Rats
Ubiquitin
IGF Type 2 Receptor
heat shock transcription factor
Angiotensin Receptor Antagonists
Cardiac Myocytes
Angiotensin II
Hypertrophy
Fingers
Apoptosis

Keywords

  • ANGII
  • HSF2
  • Hypertension
  • IGF-IIR
  • MEL18
  • SUMOylation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy. / Huang, Chih Yang; Kuo, Chia Hua; Pai, Pei Ying; Ho, Tsung Jung; Lin, Yueh Min; Chen, Ray Jade; Tsai, Fuu Jen; Vijaya Padma, V.; Kuo, Wei Wen; Huang, Chih Yang.

In: International Journal of Cardiology, Vol. 257, 15.04.2018, p. 283-290.

Research output: Contribution to journalArticle

Huang, Chih Yang ; Kuo, Chia Hua ; Pai, Pei Ying ; Ho, Tsung Jung ; Lin, Yueh Min ; Chen, Ray Jade ; Tsai, Fuu Jen ; Vijaya Padma, V. ; Kuo, Wei Wen ; Huang, Chih Yang. / Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy. In: International Journal of Cardiology. 2018 ; Vol. 257. pp. 283-290.
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