MicroRNA-149-Mediated MAPK1/ERK2 Suppression Attenuates Hair Follicle Stem Cell Differentiation

Hair follicle stem cells (HFSCs) are responsible for hair growth and hair follicle regeneration. MicroRNAs have been demonstrated to be involved in the differentiation of HFSCs. Thus, this study aimed to explore the potential role of miR-149 in the differentiation of HFSCs. The isolated HFSCs were identified by flow cytometric sorting. miR-149 expression was determined during differentiation of HFSCs. Gain- and loss-of-function approaches were conducted to explore the roles of miR-149, MAPK1/ERK2, and FGF2/c-MYC in colony formation and proliferation of HFSCs. Furthermore, in vivo assays were undertaken in miR-149 knockout mice to confirm their roles in HFSC differentiation. miR-149 was found to be downregulated during HFSC differentiation, and overexpressed miR-149 restricted the proliferation and differentiation of HFSCs. miR-149 was confirmed to target and inhibit MAPK1/ERK2, which was highly expressed in and positively associated with HFSC differentiation. The MAPK1/ERK2 promotion in HFSC differentiation was achieved by augmenting expression of FGF2 and c-MYC. The in vitro effects of miR-149 were validated in in vivo experiments. Taken together, upregulated miR-149 restricted HFSC differentiation and hair growth by targeting MAPK1/ERK2 to reduce expression of FGF2 and c-MYC, which sheds light on the underlying molecular mechanism of hair growth.