MicroRNA-21a-5p regulates TGF-?1-induced myofibroblast transformation of rabbit keratocytes by targeting Smad7

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)-21a-5p and Smad7 have been reported to play an important role in the fibrosis process. However, how miR-21a-5p involves 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 protein level as well as Smad7 and miR-21a-5p at 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-β1induced myofibroblast transformation of keratocytes by targeting Smad7 at its translation stage.

Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

“…Smad7: Smad7 negatively regulates the TGF-β/Smad signaling pathway, which can competitively bind to Smad2/3 receptors and prevent Smad2/3 phosphorylation, thereby preventing TGF-β/Smad signaling pathway activation. miR-92a [ 67 ], miR-21 [ 68 ], miR-877-3p [ 69 ], and circHNRNPH1 [ 70 ] can affect the TGF-β/Smad signaling pathway by regulating the level of Smad7. In myocardial fibrosis after ischemia, circHNRNPH1 competitively binds to miR-216-5p, induces the expression of Smad7 to accelerate the degradation of TGF-β1, inhibits the migration of myofibroblasts and the expression of α-SMA and col-Ⅰ, and alleviates the progression of myocardial fibrosis.…”