miR-146a-5p acts as a negative regulator of TGF-β signaling in skeletal muscle after acute contusion

Acta Biochimica Et Biophysica Sinica
Yaying SunHao Ying

Abstract

Growing evidence suggests the importance of microRNAs (miRNAs) in stress signaling pathways. Transforming growth factor-β (TGF-β) is a potent cytokine that promotes the development of skeletal muscle fibrosis after acute contusion. However, how miRNAs are involved in TGF-β signaling and confer the robustness of TGF-β-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-β 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-β 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-β 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...Continue Reading

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Citations

Nov 5, 2017·The British Journal of Ophthalmology·Sun Young JangJin Sook Yoon
Dec 12, 2017·Acta Biochimica Et Biophysica Sinica·Xiaohua YanYe-Guang Chen
May 22, 2019·International Journal of Molecular Sciences·Ahmed IsmaeelPanagiotis Koutakis
Jul 11, 2019·Archives of Physiology and Biochemistry·Shizhe GuoJiwu Chen
Aug 16, 2019·Skeletal Muscle·Iwona Bronisz-BudzyńskaJózef Dulak
Mar 21, 2021·European Journal of Preventive Cardiology·Isabel WitvrouwenEmeline M Van Craenenbroeck
Feb 23, 2021·Clinical and Experimental Pharmacology & Physiology·Jinrong LinJiwu Chen
May 18, 2021·Genetics and Molecular Biology·Yuan FangYanchen Chu
Jul 14, 2021·Translational Vision Science & Technology·Coralia LunaPedro Gonzalez
May 18, 2018·Journal of Agricultural and Food Chemistry·Haiou PanHao Ying

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