miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy

Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy...

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Main Authors: Mailin Gan, Jianfeng Ma, Jingyun Chen, Lei Chen, Shunhua Zhang, Ye Zhao, Lili Niu, Xuewei Li, Li Zhu, Linyuan Shen
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/9/1861
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author Mailin Gan
Jianfeng Ma
Jingyun Chen
Lei Chen
Shunhua Zhang
Ye Zhao
Lili Niu
Xuewei Li
Li Zhu
Linyuan Shen
author_facet Mailin Gan
Jianfeng Ma
Jingyun Chen
Lei Chen
Shunhua Zhang
Ye Zhao
Lili Niu
Xuewei Li
Li Zhu
Linyuan Shen
author_sort Mailin Gan
collection DOAJ
description Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle atrophy. Previous studies have shown beneficial effects of genistein treatment on muscle mass and muscle atrophy, but the mechanism is not fully understood. Differential co-expression network analysis revealed that miR-222 was upregulated in multiple skeletal muscle atrophy models. Subsequent in vitro (C2C12 myoblasts) and in vivo (C57BL/6 mice) experiments showed that genistein could alleviate dexamethasone-induced muscle atrophy and downregulate the expression of miR-222 in muscle tissue and C2C12 myotubes. The dual-luciferase reporter assay system confirmed that <i>IGF1</i> is a target gene of miR-222 and is regulated by genistein. In C2C12 myotubes, both dexamethasone and miR-222 overexpression promoted muscle atrophy, however, this function was significantly reduced after genistein treatment. Furthermore, we also observed that both genistein and miR-222 antagomiR could significantly inhibit dexamethasone-induced muscle atrophy in vivo. These results suggest that miR-222 may be involved in the regulation of genistein on muscle atrophy, and genistein and miR-222 may be used to improve muscle health.
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spelling doaj.art-6daee3fbc899434a8f1164181fd1719f2023-11-23T08:59:30ZengMDPI AGNutrients2072-66432022-04-01149186110.3390/nu14091861miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle AtrophyMailin Gan0Jianfeng Ma1Jingyun Chen2Lei Chen3Shunhua Zhang4Ye Zhao5Lili Niu6Xuewei Li7Li Zhu8Linyuan Shen9Department of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Animal Science, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaSkeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle atrophy. Previous studies have shown beneficial effects of genistein treatment on muscle mass and muscle atrophy, but the mechanism is not fully understood. Differential co-expression network analysis revealed that miR-222 was upregulated in multiple skeletal muscle atrophy models. Subsequent in vitro (C2C12 myoblasts) and in vivo (C57BL/6 mice) experiments showed that genistein could alleviate dexamethasone-induced muscle atrophy and downregulate the expression of miR-222 in muscle tissue and C2C12 myotubes. The dual-luciferase reporter assay system confirmed that <i>IGF1</i> is a target gene of miR-222 and is regulated by genistein. In C2C12 myotubes, both dexamethasone and miR-222 overexpression promoted muscle atrophy, however, this function was significantly reduced after genistein treatment. Furthermore, we also observed that both genistein and miR-222 antagomiR could significantly inhibit dexamethasone-induced muscle atrophy in vivo. These results suggest that miR-222 may be involved in the regulation of genistein on muscle atrophy, and genistein and miR-222 may be used to improve muscle health.https://www.mdpi.com/2072-6643/14/9/1861genisteinmuscle atrophymiR-222<i>IGF1</i>
spellingShingle Mailin Gan
Jianfeng Ma
Jingyun Chen
Lei Chen
Shunhua Zhang
Ye Zhao
Lili Niu
Xuewei Li
Li Zhu
Linyuan Shen
miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
Nutrients
genistein
muscle atrophy
miR-222
<i>IGF1</i>
title miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
title_full miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
title_fullStr miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
title_full_unstemmed miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
title_short miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy
title_sort mir 222 is involved in the amelioration effect of genistein on dexamethasone induced skeletal muscle atrophy
topic genistein
muscle atrophy
miR-222
<i>IGF1</i>
url https://www.mdpi.com/2072-6643/14/9/1861
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