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 |
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Affiliation: | 1. Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;2. Department of Plastic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;3. Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China;1. Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 E. Clark St., Vermillion, SD 57069, USA;2. Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA;1. Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China;2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, China;1. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Linkou and Keelung, Taiwan;2. College of Medicine, Chang Gung University, Taoyuan, Taiwan;3. Department of Neurology, Chang Gung Memorial Hospital, Taipei, Linkou, Taiwan;4. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan;5. Department of Laboratory Medicine, Chang-Gung Memorial Hospital, Taoyuan County, Taiwan;6. Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan County, Taiwan |
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Abstract: | BackgroundThe 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.ObjectiveWe proposed to investigate its effect on proliferation, adhesion and migration of cultured human outer root sheath cells from central hair follicle epithelium.MethodsThese 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.ResultsOur 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.ConclusionOur results suggest a role of VEGF/VEGFR-2 beyond angiogenesis in hair follicle regulation. |
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Keywords: | VEGFR-2 Human outer root sheath cells Central hair follicle epithelium Proliferation Differentiation Migration |
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