Epidermal Growth Factor Promotes Proliferation and Migration of Follicular Outer Root Sheath Cells via Wnt/ß-Catenin Signaling.

ABSTRACT

BACKGROUND/AIMS: To investigate the effect and molecular mechanism of EGF on the growth and migration of hair follicle outer root sheath (ORS) cells. METHODS: Intact anagen hair follicles were isolated from mink skin and cultured with EGF in vitro to measure ORS daily growth. Meanwhile, purified primary ORS cells were treated or transfected with EGF, and their proliferation and migration were assessed by MTT assay and transwell assay, respectively. The signaling pathway downstream of EGF was characterized by using the Wnt/ß-catenin signaling inhibitor, XAV-939. RESULTS: EGF of 2-20 ng/ml, not higher or lower, promoted the growth of follicular ORS in vitro. EGF treatment or overexpression promoted the proliferation and migration of ORS cells. Moreover, EGF stimulation induced nuclear translocation of ß-catenin, and upregulated the expression of Wnt10b, ß-catenin, EGF receptor and SOX9. Inhibition of Wnt/ß-catenin signaling by XAV-939 significantly reduced the basal and EGF-enhanced proliferation and migration of ORS cells. In addition, a number of follicle-regulatory genes, such as Survivin, Msx2 and SGK3, were upregulated by EGF in the ORS cells, which was also inhibited by XAV-939. CONCLUSION: EGF promotes the proliferation and migration of ORS cells and modulates the expression of several follicle-regulatory genes via Wnt/ß-catenin signaling.