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.