VEGF upregulates VEGF receptor-2 on human outer root sheath cells and stimulates proliferation through ERK pathway.
Vascular endothelial growth factor (VEGF) is a key regulator of physiological and pathological angiogenesis. The biological effects of VEGF are mediated by receptor tyrosine kinases. VEGF receptor-2, the primary receptor for VEGF, is thought to mediate most functional effects. In this study, we examined the expression and roles of VEGF receptor-2 on human outer root sheath cells (ORS). The expression of VEGFR-2 was determined at mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Localization of VEGFR-2 in ORS cells was detected by immunofluorescence. The effect of VEGF on ORS cell proliferation was determined by MTT assays. Our data showed the expression of VEGFR-2 on ORS cells at both mRNA and protein levels. Immunostaining for VEGFR-2 demonstrated strong signal on cultured ORS cells. Exogenous VEGF(165) stimulated proliferation of ORS cells and upregulated expression of VEGFR-2 in a dose-dependent manner. Moreover, VEGF(165) induced phosphorylation of VEGFR-2, PLC-γ1, PKC-α, MEK, and p44/42 MAPK (ERK1/2) in a time-dependent manner. Taken together, human ORS cells express functional VEGF receptor-2 and exogenous VEGF(165) upregulates expression of VEGFR-2 and stimulates proliferation of ORS cells via VEGFR-2 mediated ERK signaling pathway.
Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China.
Wei
W
Li
Zhong-Fa
ZF
Lu
Xiao-Yong
XY
Man
Chun-Ming
CM
Li
Jiong
J
Zhou
Jia-Qi
JQ
Chen
Xiao-Hong
XH
Yang
Xian-Jie
XJ
Wu
Sui-Qing
SQ
Cai
Min
M
Zheng
D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018859:Hair Follicle / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051571:Protein Kinase C-alpha; D051966:Phospholipase C gamma