title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  Our results suggest a role of VEGF/VEGFR-2 beyond angiogenesis in hair follicle regulation.
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: wuxianjie163@163.com.
authors.forename: Xian-Jie
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: 15306570957@189.cn.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: haitong1987@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Jing
authors.affiliation: Department of Plastic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: xxuueeddaann@sohu.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Xue
authors.affiliation: Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: liuhai6733@163.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: minzju@gmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: lzfskin@163.com.
authors.forename: Zhong-Fa
authors.initials: ZF
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D008875:Middle Aged; D010766:Phosphorylation; D012535:Scalp / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000906:Antibodies; D019012:Integrin beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: 4,6-diamidino-2-phenylindole; Central hair follicle epithelium; DAPI; DP; DPC; Differentiation; ERK; Human outer root sheath cells; IRS; Jun; Migration; NRP; ORS; PKC-a; PLC-c; Proliferation; RT-PCR; VEGFR; VEGFR-2; extracellular signal-regulated kinase; hair follicle dermal papilla; hair follicle dermal papilla cell; inner root sheath; jun oncogene; neuropilin; outer root sheath; p38; p38-mitogen-activated protein kinase; phospholipase C-c; protein kinase C-a; reverse transcript polymerase chain reaction; vascular endothelial growth factor receptor