miR-24 and miR-122 Negatively Regulate the Transforming Growth Factor-β/Smad Signaling Pathway in Skeletal Muscle Fibrosis

被引：82

作者：

Sun, Yaying ^{[1
]}

Wang, Hui ^{[2
]}

Li, Yan ^{[2
,3
]}

Liu, Shaohua ^{[1
]}

Chen, Jiwu ^{[1
]}

Ying, Hao ^{[2
]}

机构：

[1] Fudan Univ, Huashan Hosp, Dept Sports Med, 12 Middle Wulumuqi Rd, Shanghai 200040, Peoples R China

[2] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Food Safety Res, Shanghai, Peoples R China

[3] Jiangnan Univ, Sch Food Sci & Technol, State Key Lab Food Sci & Technol, Wuxi 214122, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2018年 / 11卷

基金：

中国国家自然科学基金;

关键词：

TGF-BETA; ACUTE CONTUSION; MOUSE MODEL; STEM-CELLS; LIVER FIBROSIS; INJURY; DIFFERENTIATION; REGENERATION; METASTASIS; IMPROVES;

D O I：

10.1016/j.omtn.2018.04.005

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Fibrosis is common after skeletal muscle injury, undermining tissue regeneration and function. The mechanism underlying skeletal muscle fibrosis remains unveiled. Transforming growth factor-beta/Smad signaling pathway is supposed to play a pivotal role. However, how microRNAs interact with transforming growth factor-beta/Smad-related muscle fibrosis remains unclear. We showed that microRNA (miR)-24-3p and miR-122-5p declined in skeletal muscle fibrosis, which was a consequence of transforming growth factor-beta. Upregulating Smad4 suppressed two microRNAs, whereas inhibiting Smad4 elevated microRNAs. Luciferase reporter assay and chromatin immunoprecipitation confirmed that Smad4 directly inhibited two microRNAs. On the other hand, overexpression of these two miRs retarded fibrotic process. We further identified that Smad2 was a direct target of miR-24-3p, whereas miR-122-5p targeted transforming growth factor-beta receptor-II. Both targets were important participants in transforming growth factor-beta/Smad signaling. Taken together, a positive feedback loop in transforming growth factor-beta/Smad4 signaling pathway in skeletal muscle fibrosis was identified. Transforming growth factor-beta/Smad axis could be downregulated by microRNAs. This effect, however, was suppressed by Smad4, the downstream of transforming growth factor-beta.

引用

页码：528 / 537

页数：10

共 57 条

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