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

研究成果: 雜誌貢獻文章

10 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)283-290
期刊International Journal of Cardiology
257
DOIs
出版狀態已發佈 - 四月 15 2018

    指紋

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

引用此

Huang, C. Y., Kuo, C. H., Pai, P. Y., Ho, T. J., Lin, Y. M., Chen, R. J., Tsai, F. J., Vijaya Padma, V., Kuo, W. W., & Huang, C. Y. (2018). Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy. International Journal of Cardiology, 257, 283-290. https://doi.org/10.1016/j.ijcard.2017.10.102