Abstract
Hypertrophic scar (HS) is a severe skin disorder characterized by excessive extracellular matrix production and abnormal function of fibroblasts. Recent studies have demonstrated that microRNAs (miRNAs) play critical roles in HS formation. This study aims to investigate the role of miR-3613-3p in the formation of HS. The mRNA and miRNA levels were measured by quantitative RT-PCR analysis. The protein levels were examined by Western blot assay. Cell proliferation was determined by Cell Counting Kit-8 assay. The Caspase-3 and Caspase-9 activities were measured using flow cytometry assay. Dual-luciferase activity reporter assay and mRNA-miRNA pulldown assay were conducted to validate the target of miR-3613-3p. miR-3613-3p was downregulated, while arginine and glutamate-rich 1 (ARGLU1) was upregulated in HS fibroblasts (HSFs) and tissues. Overexpression of miR-3613-3p or knockdown of ARGLU1 markedly inhibited the expression of extracellular matrix (ECM) production-associated proteins and promoted Caspase-3 and Caspase-9 activations in HSFs. ARGLU1 was further identified as a direct target of miR-3613-3p. Restoration of ARGLU1 abrogated the suppressive effect of miR-3613-3p on cell proliferation and ECM protein expression of HSFs. Our results demonstrated that miR-3613-3p inhibited HS formation via targeting ARGLU1, which may provide potential therapeutic targets for the management of HS.
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