miR-203a-3p promotes loureirin A-induced hair follicle stem cells differentiation by targeting Smad1

Abstract

MicroRNAs (miRNAs) participate in the repair of skin trauma. Our previous study indicated that loureirin A promoted hair follicle stem cells (HFSCs) to repair skin epidermis. However, the mechanism of miRNA-mediated regulation of loureirin A-induced HFSC differentiation remained to be explored. In the present study, HFSCs from rat vibrissa were identified by immunofluorescence in vitro. Microarray and quantitative real time polymerase chain reaction analyses demonstrated that miR-203a-3p was upregulated in differentiated HFSCs induced by loureirin A. The expression of cytoskeletal keratin (CK) 5 and involucrin was promoted by miR-203a-3p mimics while repressed by a miR-203a-3p inhibitor. Smad1 was identified as a key target of miR-203a-3p using target prediction tools. Luciferase reporter gene test confirmed a special target association between miR-203a-3p and Smad1. Short interfering Smad1 was transfected into HFSCs, and the expression levels of CK5 and involucrin were upregulated. Thus, it can be inferred that miR-203a-3p negatively regulated the expression of Smad1 and promoted the differentiation of loureirin A-induced HFSCs. Bone morphogenetic protein (BMP) signal inhibition and Wnt activation coregulate skin injury repair. BMP/Smad1 signaling is involved in maintaining the characteristics of HFSCs and inhibiting their differentiation. Our results showed that miR-203a-3p reduces Smad1 to release BMP inhibition. Taken together, miR-203a-3p/Smad1 is a potential therapeutic molecular target in skin wound healing, and may play an active role in wound repair and regenerative medicine.