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

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

Published: 5 March 2021


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.

Full Access Link: Molecular Therapy - Nucleic Acids