A novel regulatory function for miR-29a in keloid fibrogenesis

Background. A growing body of evidence has shown that microRNA-29 (miR-29) plays a central role in the progression of fibrosis. However, the mechanisms underlying the role of miR-29 in keloid fibrogenesis remain unknown. Aim. To investigate the roles of miR-29 in dermal fibroblasts in the pathogenesis of keloids. Methods. Primary fibroblasts from 9 patients with keloid and 6 healthy controls (HCs) were cultured and pretreated with transforming growth factor (TGF)-beta 1. Next, fibroblasts were transfected with precursor miRNA and anti-miR-29a miRNA. TGF-beta 1-associated miR-29 alterations were investigated by quantitative real-time PCR. Collagen I and collagen III protein levels were analysed by western blotting. Results. miR-29a, miR-29b and miR-29c levels were significantly lower in keloid compared with healthy fibroblasts (P < 0.05), and in particular, miR-29a was especially markedly reduced (P < 0.001). Type I and type III collagen mRNA and protein levels were decreased in keloid fibroblasts transfected with pre-miR-29a (P < 0.05), whereas knockdown with anti-miR-29a increased type I and type III collagen mRNA and protein expression (P < 0.05) in the fibroblasts. Interestingly, pretreatment of fibroblasts with TGF-beta 1 significantly decreased miR-29a (P < 0.05), whereas miR-29b and miR-29c were reduced to a lesser extent, which was not significant. Conclusions. These findings show that miR-29a exerts as a novel regulator in the fibrogenesis of keloid, suggesting that miR-29a might be a novel marker for keloid.