Angiotensin II-induced muscle atrophy via PPAR gamma 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 PPAR gamma 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	743-756
Number of pages	14
Journal	Molecular Therapy - Nucleic Acids
Volume	23
DOIs	https://doi.org/10.1016/j.omtn.2020.12.015
Publication status	Published - 5 Mar 2021

Keywords

angiotensin II
miR-29b
muscle atrophy
PPARγ

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10.1016/j.omtn.2020.12.015Licence: CC BY-NC-ND

1-s2.0-S2162253120303966-mainFinal published version, 5.1 MBLicence: CC BY-NC-ND

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@article{8dbea848facf4e079490194b6c3ae917,

title = "Angiotensin II-induced muscle atrophy via PPAR gamma suppression is mediated by miR-29b",

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 = "angiotensin II, miR-29b, muscle atrophy, PPARγ",

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

note = "Funding Information: This work was supported by the grants from Innovation Program of Shanghai Municipal Education Commission ( 2017-01-07-00-09-E00042 to J.X.); National Key Research and Development Project ( 2018YFE0113500 to J.X.); National Natural Science Foundation of China ( 82020108002 , 81722008 , and 81911540486 to J.X. and 81900359 to J.L.); a grant from Science and Technology Commission of Shanghai Municipality ( 18410722200 and 17010500100 to J.X.); the “Dawn” Program of Shanghai Education Commission (19SG34 to J.X.); Shanghai Sailing Program ( 19YF1416400 to J.L.); “Chen Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation ( 19CG45 to J.L.); and the National Institutes of Health (grants UH3 TR000901 and HL122547 to S.D.). J.P.G.S. is supported by Horizon2020 ERC-2016-COG EVICARE ( 725229 ), Technobeat ( 668724 ), and Vrienden UMC Utrecht. Funding Information: This work was supported by the grants from Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to J.X.); National Key Research and Development Project (2018YFE0113500 to J.X.); National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to J.X. and 81900359 to J.L.); a grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to J.X.); the ?Dawn? Program of Shanghai Education Commission (19SG34 to J.X.); Shanghai Sailing Program(19YF1416400 to J.L.); ?Chen Guang? project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (19CG45 to J.L.); and the National Institutes of Health (grants UH3 TR000901 and HL122547 to S.D.). J.P.G.S. is supported by Horizon2020 ERC-2016-COG EVICARE (725229), Technobeat (668724), and Vrienden UMC Utrecht., J.X. and L.Y. designed the study and instructed all experiments. J.X. drafted the manuscript. J.L, T.Y. Z.S. H.T. X.H. L.W. Z.W. and Z.G. performed the experiments and analyzed the data. J.P.G.S. G.C.R. and S.D. provided technical assistance and revised the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = mar,

day = "5",

doi = "10.1016/j.omtn.2020.12.015",

language = "English",

volume = "23",

pages = "743--756",

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T1 - Angiotensin II-induced muscle atrophy via PPAR gamma suppression is mediated by miR-29b

AU - Li, Jin

AU - Yang, Tingting

AU - Sha, Zhao

AU - Tang, Haifei

AU - Hua, Xuejiao

AU - Wang, Lijun

AU - Wang, Zitong

AU - Gao, Ziyu

AU - Sluijter, Joost P.G.

AU - Rowe, Glenn C.

AU - Das, Saumya

AU - Yang, Liming

AU - Xiao, Junjie

N1 - Funding Information: This work was supported by the grants from Innovation Program of Shanghai Municipal Education Commission ( 2017-01-07-00-09-E00042 to J.X.); National Key Research and Development Project ( 2018YFE0113500 to J.X.); National Natural Science Foundation of China ( 82020108002 , 81722008 , and 81911540486 to J.X. and 81900359 to J.L.); a grant from Science and Technology Commission of Shanghai Municipality ( 18410722200 and 17010500100 to J.X.); the “Dawn” Program of Shanghai Education Commission (19SG34 to J.X.); Shanghai Sailing Program ( 19YF1416400 to J.L.); “Chen Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation ( 19CG45 to J.L.); and the National Institutes of Health (grants UH3 TR000901 and HL122547 to S.D.). J.P.G.S. is supported by Horizon2020 ERC-2016-COG EVICARE ( 725229 ), Technobeat ( 668724 ), and Vrienden UMC Utrecht. Funding Information: This work was supported by the grants from Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to J.X.); National Key Research and Development Project (2018YFE0113500 to J.X.); National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to J.X. and 81900359 to J.L.); a grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to J.X.); the ?Dawn? Program of Shanghai Education Commission (19SG34 to J.X.); Shanghai Sailing Program(19YF1416400 to J.L.); ?Chen Guang? project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (19CG45 to J.L.); and the National Institutes of Health (grants UH3 TR000901 and HL122547 to S.D.). J.P.G.S. is supported by Horizon2020 ERC-2016-COG EVICARE (725229), Technobeat (668724), and Vrienden UMC Utrecht., J.X. and L.Y. designed the study and instructed all experiments. J.X. drafted the manuscript. J.L, T.Y. Z.S. H.T. X.H. L.W. Z.W. and Z.G. performed the experiments and analyzed the data. J.P.G.S. G.C.R. and S.D. provided technical assistance and revised the manuscript. The authors declare no competing interests. Publisher Copyright: © 2020 The Authors

PY - 2021/3/5

Y1 - 2021/3/5

N2 - 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.

AB - 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.

KW - angiotensin II

KW - miR-29b

KW - muscle atrophy

KW - PPARγ

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U2 - 10.1016/j.omtn.2020.12.015

DO - 10.1016/j.omtn.2020.12.015

M3 - Article

C2 - 33614226

AN - SCOPUS:85100383966

SN - 2162-2531

VL - 23

SP - 743

EP - 756

JO - Molecular Therapy - Nucleic Acids

JF - Molecular Therapy - Nucleic Acids

ER -

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

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Keywords

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