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...
Main Authors: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1818728576678100992 |
---|---|
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. |
first_indexed | 2024-12-17T22:32:12Z |
format | Article |
id | doaj.art-fb5b5e2ec8684f928f7ab33f08f6311d |
institution | Directory Open Access Journal |
issn | 2162-2531 |
language | English |
last_indexed | 2024-12-17T22:32:12Z |
publishDate | 2021-03-01 |
publisher | Elsevier |
record_format | Article |
series | Molecular Therapy: Nucleic Acids |
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 |
work_keys_str_mv | AT jinli angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT tingtingyang angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT zhaosha angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT haifeitang angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT xuejiaohua angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT lijunwang angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT zitongwang angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT ziyugao angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT joostpgsluijter angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT glenncrowe angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT saumyadas angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT limingyang angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b AT junjiexiao angiotensiniiinducedmuscleatrophyviappargsuppressionismediatedbymir29b |