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
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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 |
DOI | 10.1093/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, |
推荐引用方式 GB/T 7714 | 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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