miR-181b-5p promotes proliferation and inhibits apoptosis of hypertrophic scar fibroblasts through regulating the MEK/ERK/p21 pathway

Exp Ther Med. 2019 Mar;17(3):1537-1544. doi: 10.3892/etm.2019.7159. Epub 2019 Jan 7.


Hypertrophic scar (HS) is a common skin disorder occurring during the wound healing process, and the pathogenesis of HS remains unclear. Previous studies indicated that miRNAs may be involved in the onset and progression of HS. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to investigate the expression of miR-181b-5p and decorin in HS tissues. Direct interaction between miR-181b-5p and decorin was confirmed using a dual-luciferase assay. Human HS fibroblasts (HSFbs) were cultured and transfected with miR-181b-5p mimics, and MTT assay and Annexin V fluorescein isothiocyanate/propidium iodide staining were performed to investigate the role of miR-181b-5p in the proliferation and apoptosis of HSFbs. Subsequently, the expression levels of mitogen-activated protein kinase kinase (MEK), phospho (p)-extracellular signal-regulated kinase (ERK) and p21 were determined in HSFbs transfected with miR-181b-5p mimics and untransfected cells using RT-qPCR and western blotting. The results indicated upregulation of miR-181b-5p and downregulation of decorin expression in HS tissues compared with normal skin samples. miR-181b-5p may regulate the expression of decorin through direct binding to the 3'-untranslated region, as demonstrated by the results of the dual-luciferase assay. Transfection with miR-181b-5p mimics in HSFbs enhanced cell proliferation, reduced apoptosis and increased the expression of MEK, p-ERK and p21. Furthermore, treatment with MEK inhibitor in HSFbs transfected with miR-181b-5p mimics partially inhibited miR-181b-5p-induced antiapoptotic effects. Taken together, increased expression of miR-181b-5p may serve important roles in the pathogenesis of HS through regulating the MEK/ERK/p21 pathway, suggesting that miR-181b-5p may be a therapeutic target for the treatment of HS.

Keywords: apoptosis; decorin; hypertrophic fibroblasts; microRNA-181b-5p; mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/p21 pathway; proliferation.