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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2021-03-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253120303966
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author 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
author_facet 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
author_sort Jin Li
collection DOAJ
description 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.
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spelling doaj.art-fb5b5e2ec8684f928f7ab33f08f6311d2022-12-21T21:30:11ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-03-0123743756Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29bJin Li0Tingting Yang1Zhao Sha2Haifei Tang3Xuejiao Hua4Lijun Wang5Zitong Wang6Ziyu Gao7Joost P.G. Sluijter8Glenn C. Rowe9Saumya Das10Liming Yang11Junjie Xiao12Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, ChinaDepartment of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, ChinaDepartment of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, ChinaDepartment of Cardiology, Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht 3508GA, the Netherlands; UMC Utrecht Regenerative Medicine Center, University Medical Center, Utrecht University, Utrecht 3508GA, the NetherlandsDepartment of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USACardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA 02215, USADepartment of Pathophysiology, Harbin Medical University-Daqing, Daqing, 163319, China; Corresponding author: Liming Yang, Department of Pathophysiology, Harbin Medical University-Daqing, Daqing, 163319, China.Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China; Corresponding author: Junjie Xiao, Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444, China.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.http://www.sciencedirect.com/science/article/pii/S2162253120303966muscle atrophyangiotensin IIPPARγmiR-29b
spellingShingle 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
Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b
Molecular Therapy: Nucleic Acids
muscle atrophy
angiotensin II
PPARγ
miR-29b
title Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b
title_full Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b
title_fullStr Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b
title_full_unstemmed Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b
title_short Angiotensin II-induced muscle atrophy via PPARγ suppression is mediated by miR-29b
title_sort angiotensin ii induced muscle atrophy via pparγ suppression is mediated by mir 29b
topic muscle atrophy
angiotensin II
PPARγ
miR-29b
url http://www.sciencedirect.com/science/article/pii/S2162253120303966
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