MicroRNA-26a inhibits hyperplastic scar formation by targeting Smad2.

Abstract

Hypertrophic scar (HS) is a fibrotic disease in which excessive extracellular matrix forms due to the response of fibroblasts to tissue damage. Novel evidence suggests that microRNAs (miRNAs or miRs) may contribute to hypertrophic scarring; however, the role of miRNAs in HS formation remains unclear. In the present study, miR-26a was significantly downregulated in HS tissues and human HS fibroblasts (hHSFs) was detected by reverse transcription-quantitative analysis. TargetScan was used to predict that mothers against decapentaplegic homolog 2 (Smad2) is a potential target gene of miR-26a and a dual-luciferase reporter assay confirmed that Smad2 was a target gene of miR-26a. The expression of Smad2 was upregulated in HS tissues and hHSFs. Cell Counting Kit-8 and flow cytometry analyses demonstrated that the overexpression of miR-26a significantly suppressed the proliferation ability of hHSFs and the apoptotic rate of hHSFs was significantly upregulated in response to miR-26a mimic transfection. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2)-associated X protein was increased and Bcl-2 expression was decreased following miR-26a mimic transfection. The expression of collagens I and III was significantly inhibited following treatment with miR-26a mimics in hHSF cells. Conversely, miR-26a inhibitors served an opposing role in hHSFs. Furthermore, Smad2 overexpression enhanced the expression of collagens I and c III; however, Smad2 silencing inhibited the expression of collagens I and c III. In conclusion, the results of the present study indicate that miR-26a inhibits HS formation by modulating proliferation and apoptosis ad well as inhibiting the expression of extracellular matrix-associated proteins by targeting Smad2.