MicroRNA-202-3p regulates scleroderma fibrosis by targeting matrix metalloproteinase 1

Abstract

The leading cause of death in systemic sclerosis (SSc) is the uncontrolled fibrosis in multiple organs. The exact mechanism of fibrosis is not fully clear. Our previous studies using miRNA array analysis indicated that miR-202-3p was increased in SSc lesion skin tissues. Bioinformatics analysis suggested matrix metallopeptidase (MMP) 1 is the target gene of miR-202-3p. Here we confirmed that miR-202-3p was upregulated, and the mRNA and protein expression of MMP1 were significantly decreased in SSc skin tissues and primary fibroblast compared with normal skin. MMP1 expression was inversely correlated with the expression of miR-202-3p. Overexpression of miR-202-3p markedly increased collagen disposition in skin primary fibroblasts, while inhibitor of miR-202-3p decreased it. Furthermore, we demonstrated that MMP1 was a target of miR-202-3p detected by luciferase reporter assay, and played an essential role as a mediator of the biological effects of miR-202-3p in SSc fibrosis. Taken together, these findings suggest that miR-202-3p may function as a novel pro-fibrotic miRNA in SSc by inhibition the expression of MMP1.

Keywords: Fibrosis; MMP1; Systemic sclerosis; miR-202-3p.