VEGF165 modulates proliferation, adhesion, migration and differentiation of cultured human outer root sheath cells from central hair follicle epithelium through VEGFR-2 activation in vitro

摘要

Background: The functional state of vasculature is tightly controlled by vascular endothelial growth factor receptor-2 (VEGFR-2). Recent studies revealed that VEGFR-2 is expressed on hair follicle keratinocytes. Objective: We proposed to investigate its effect on proliferation, adhesion and migration of cultured human outer root sheath cells from central hair follicle epithelium. Methods: These studies were undertaken in vitro using human outer root sheath cells from central hair follicle epithelium, immunohistochemistry analysis, immunofluorescence microscopy, western blot analysis, MTT, trans well analysis, and RT-PCR. Results: Our results show that VEGFR-2 is expressed in these cells in vivo and in vitro. Furthermore, proliferation and migration of cultured human outer root sheath cells from central hair follicle epithelium is increased by VEGF165, while homotypic adhesion is decreased but heterotypic adhesion is increased. VEGF165 upregulates integrin β1 but dowregulates lgr6 expression. In addition, phosphorylation of VEGFR-2, Erk1/2, c-Jun and p38, are increased following VEGF165 treatment and these effects are reversed by a VEGFR-2 neutralizing antibody. Conclusion: Our results suggest a role of VEGF/VEGFR-2 beyond angiogenesis in hair follicle regulation.