Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b

Jin Li; Tingting Yang; Zhao Sha; Haifei Tang; Xuejiao Hua; Lijun Wang; Zitong Wang; Ziyu Gao; Joost P G Sluijter; Glenn C Rowe; Saumya Das; Liming Yang; Junjie Xiao

doi:10.1016/j.omtn.2020.12.015

Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b

Mol Ther Nucleic Acids. 2020 Dec 25:23:743-756. doi: 10.1016/j.omtn.2020.12.015. eCollection 2021 Mar 5.

Authors

Jin Li¹, Tingting Yang¹, Zhao Sha¹, Haifei Tang¹, Xuejiao Hua¹, Lijun Wang¹, Zitong Wang², Ziyu Gao², Joost P G Sluijter^{3

4}, Glenn C Rowe⁵, Saumya Das⁶, Liming Yang⁷, Junjie Xiao¹

Affiliations

¹ Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.
² Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China.
³ Department of Cardiology, Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht 3508GA, the Netherlands.
⁴ UMC Utrecht Regenerative Medicine Center, University Medical Center, Utrecht University, Utrecht 3508GA, the Netherlands.
⁵ Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁶ Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA 02215, USA.
⁷ Department of Pathophysiology, Harbin Medical University-Daqing, Daqing, 163319, China.

Abstract

The activation of the renin-angiotensin system (RAS) induced by increased angiotensin II (AngII) levels has been implicated in muscle atrophy, which is involved in the pathogenesis of congestive heart failure. Although peroxisome proliferator-activated receptor gamma (PPARγ) activation can suppress RAS, the exact role of PPARγ in AngII-induced muscle atrophy is unclear. Here we identified PPARγ as a negative regulator of miR-29b, a microRNA that is able to promote multiple types of muscle atrophy. Suppression of miR-29b could prevent AngII-induced muscle atrophy both in vitro and in vivo. IGF1, PI3K(p85α), and Yin Yang 1 (YY1) were identified as target genes of miR-29b, and overexpression of these targets could rescue AngII-induced muscle atrophy. Importantly, inhibition of PPARγ was sufficient to induce muscle atrophy, while PPARγ overexpression could attenuate that. These data indicate that the PPARγ/miR-29b axis mediates AngII-induced muscle atrophy, and increasing PPARγ or inhibiting miR-29b represents a promising approach to counteract AngII-induced muscle atrophy.

Keywords: PPARγ; angiotensin II; miR-29b; muscle atrophy.

Abstract

Grants and funding