MicroRNA 322 Aggravates Dexamethasone-Induced Muscle Atrophy by Targeting IGF1R and INSR

被引:18
|
作者
Geng, Hongwei [1 ]
Song, Qinglong [2 ,3 ]
Cheng, Yunyun [1 ]
Li, Haoyang [1 ]
Yang, Rui [1 ]
Liu, Songcai [1 ,4 ]
Hao, Linlin [1 ]
机构
[1] Jilin Univ, Coll Anim Sci, Changchun 130062, Peoples R China
[2] China Agr Univ, State Key Lab Anim Nutr, Beijing 100193, Peoples R China
[3] Beijing Key Lab Biofeed Additives, Beijing 100193, Peoples R China
[4] Five Star Anim Hlth Pharmaceut Factory Jilin Prov, Changchun 130062, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-322; dexamethasone; IGF1R; INSR; atrophy; skeletal muscle; SKELETAL-MUSCLE; MECHANISMS;
D O I
10.3390/ijms21031111
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dexamethasone (Dex) has been widely used as a potent anti-inflammatory, antishock, and immunosuppressive agent. However, high dose or long-term use of Dex is accompanied by side effects including skeletal muscle atrophy, whose underlying mechanisms remain incompletely understood. A number of microRNAs (miRNAs) have been shown to play key roles in skeletal muscle atrophy. Previous studies showed significantly increased miR-322 expression in Dex-treated C2C12 myotubes. In our study, the glucocorticoid receptor (GR) was required for Dex to increase miR-322 expression in C2C12 myotubes. miR-322 mimic or miR-322 inhibitor was used for regulating the expression of miR-322. Insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (INSR) were identified as target genes of miR-322 using luciferase reporter assays and played key roles in Dex-induced muscle atrophy. miR-322 overexpression promoted atrophy in Dex-treated C2C12 myotubes and the gastrocnemius muscles of mice. Conversely, miR-322 inhibition showed the opposite effects. These data suggested that miR-322 contributes to Dex-induced muscle atrophy via targeting of IGF1R and INSR. Furthermore, miR-322 might be a potential target to counter Dex-induced muscle atrophy. miR-322 inhibition might also represent a therapeutic approach for Dex-induced muscle atrophy.
引用
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页数:14
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