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MicroRNA-21a-5p regulates TGF-β1-induced myofibroblast transformation of rabbit keratocytes by targeting Smad7

Jianhai Bai^a, Minli Zhang^b, Xiaomin Ding^b, Xingzhi Yang^b, Dan Zheng^a, Hongyun Mou^a, Xiaoxiao Ruan^a, Yueqing Feng^c, Haifei Hanb, Shili Wang^a,*

 
ABSTRACT:     The transforming growth factor β1 (TGF-β1)-induced transformation of keratocytes to myofibroblasts is a very common process during corneal wound healing, but a dysregulated TGF-β1 activity may induce unfavorable fibrosis and scar formation in the cornea. MicroRNA (miR replica watches)-21a-5p and Smad7 have been reported to play an important role in the fibrosis process. However, how miR-21a-5p is involved in the TGF-β1-induced myofibroblasts transformation of keratocytes remains unclear. In the present study, we found an increase in the expressions of α-SMA and collagen I at the protein level as well as Smad7 and miR-21a-5p at the mRNA level when keratocytes were treated with TGF-β1Here; but the Smad7 at protein level kept unchanged. The overexpression of miR-21a-5p attenuated Smad7 protein expression, and miR-21a-5p inhibition promoted Smad7 protein expression without affecting its mRNA expression. Furthermore, inhibition of miR-21a-5p could decrease TGF-β1-induced α-SMA expression, whereas the addition of Smad7 knockdown would rescue the expression of α-SMA. These results suggested that miR-21a-5p had a promoting effect on TGF-β1-induced myofibroblast transformation of keratocytes by targeting Smad7 at its translation stage.

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* Corresponding author, E-mail: wangsl7149@tzzxyy.com

Received 29 Jan 2021, Accepted 27 Aug 2021