中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle after acute contusion

文献类型:期刊论文

作者Sun, Yaying1; Li, Hongyun1; Liu, Shaohua1; Chen, Jiwu1; Li, Yan2; Wang, Hui2; Ying, Hao2; ,
刊名ACTA BIOCHIMICA ET BIOPHYSICA SINICA
出版日期2017
卷号49期号:7页码:628-634
关键词microRNA transforming growth factor-beta Smad4 fibrosis muscle
ISSN号1672-9145
DOI10.1093/abbs/gmx052
文献子类Article
英文摘要Growing evidence suggests the importance of microRNAs (miRNAs) in stress signaling pathways. Transforming growth factor-beta (TGF-beta) is a potent cytokine that promotes the development of skeletal muscle fibrosis after acute contusion. However, how miRNAs are involved in TGF-beta signaling and confer the robustness of TGF-beta-induced fibrotic response remains to be fully elucidated. Here, we demonstrated that miR-146a-5p (miR-146) levels were reduced in a fibrotic mouse model after acute muscle contusion. It was also found that TGF-beta treatment decreased the expression of miR-146 in vitro in a dose-and time-dependent manner. In addition, overexpression of Smad3 and Samd4, two key players in TGF-beta signaling, suppressed the expression of miR-146 in muscle cells. Overexpression of miR-146 inhibited the expressions of fibrosis markers both in vitro and in vivo. Moreover, increase in the expression of miR-146 in muscle cells was able to attenuate the effect of TGF-beta on the expressions of fibrosis markers. Mechanistic analysis revealed that Smad4 is a direct target of miR-146 in muscle cells. Furthermore, the anti-fibrotic effect of miR-146 could be blocked by overexpression of Smad4 in vivo. These results suggest that Smad4 is down-regulated by miR-146 in skeletal muscle. Taken together, our results indicate that the anti-fibrotic miR-146 is a component of TGF-beta signaling. It is down-regulated by Smad protein, and can inhibit the expression of Smad4. Our study suggests that miR-146 might have a therapeutic potential to reduce skeletal muscle fibrosis after injury.
学科主题Biochemistry & Molecular Biology ; Biophysics
WOS关键词HUMAN DERMAL FIBROBLASTS ; FIBROSIS IN-VIVO ; DOWN-REGULATION ; MOUSE MODEL ; MICRORNA-146A ; INJURY ; DIFFERENTIATION ; CELLS ; SMAD4 ; REGENERATION
语种英语
WOS记录号WOS:000404955800008
出版者OXFORD UNIV PRESS
版本出版稿
源URL[http://202.127.25.144/handle/331004/796]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Fudan Univ, Huashan Hosp, Dept Sports Med, Shanghai 200040, Peoples R China;
2.Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci, Key Lab food safety Res,Inst Nutr Sci, Shanghai 200031, Peoples R China,
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Sun, Yaying,Li, Hongyun,Liu, Shaohua,et al. miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle after acute contusion[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2017,49(7):628-634.
APA Sun, Yaying.,Li, Hongyun.,Liu, Shaohua.,Chen, Jiwu.,Li, Yan.,...&,.(2017).miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle after acute contusion.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,49(7),628-634.
MLA Sun, Yaying,et al."miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle after acute contusion".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 49.7(2017):628-634.

入库方式: OAI收割

来源:上海营养与健康研究所

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