Hsa-miR-425-5p Inhibits Hypertrophic Scar Formation Through Suppressing the Growth of Human Hypertrophic Scar Fibroblasts and Extracellular Matrix Deposition by Targeting Smad2

Abstract

The current study aimed to explore the role and mechanism of microRNA-425-5p (miR-425-5p) in hypertrophic scar (HS) development. Firstly, we used reverse transcription-quantitative polymerase chain reaction (qRT-PCR)to detect the expression of miR-425-5p in human hypertrophic scar fibroblasts (hHSFs) and HS tissues. qRT-PCR assay showed that miR-425-5p level significantly down-regulated in HS tissues and hHSFs. Next, we performed TargetScan and dual-luciferase reporter assay to predict and verify Smad2 was the target gene of miR-425-5p. In order to determine the role of miR-425-5p in HS formation, miR-425-5p was over-expressed or knockdown in hHSFs through transfection with miR-425-5p mimic or miR-425-5p inhibitor. CCK-8 assay and cell apoptosis analysis were carried out to measure cell viability and apoptosis. Protein expression was assessed by Western blotting. The findings indicated that miR-425-5p mimic transfection inhibited cell viability, promoted cell apoptosis and repressed Smad2, Col I, and Col III expression in hHSFs. Notably, the transfection of Smad2-plasmid eliminated the effects of miR-425-5p mimic on hHSFs. However, miR-425-5p inhibitor transfection had opposite effects on hHSFs, and were eliminated by the transfection of Smad2-siRNA. In conclusion, these findings suggested that miR-425-5p inhibited the hHSFs viability, induced hHSFs apoptosis and repressed extracellular matrix deposition of hHSFs through regulating Smad2. Therefore, miR-425-5p might be a novel therapeutic target for HS treatment.