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论文题目: miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle after acute contusion
英文论文题目: miR-146a-5p acts as a negative regulator of TGF-beta signaling in skeletal muscle after acute contusion
第一作者: Sun, YY; Li, Y; Wang, H; Li, HY; Liu, SH; Chen, JW; Ying, H
英文第一作者: Sun, YY; Li, Y; Wang, H; Li, HY; Liu, SH; Chen, JW; Ying, H
联系作者: Ying, H (reprint author), Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci, Key Lab Food Safety Res,Inst Nutr Sci, Shanghai 200031, Peoples R China.
英文联系作者: Ying, H (reprint author), 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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发表年度: 2017
卷: 49
期: 7
页码: 628-634
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.
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.
刊物名称: ACTA BIOCHIMICA ET BIOPHYSICA SINICA
英文刊物名称: ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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学科: Biochemistry & Molecular Biology; Biophysics
英文学科: Biochemistry & Molecular Biology; Biophysics
影响因子: 2.2
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论文类别: Article
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