VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK
VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK
复制标题
VEGF 通过 VEGFR-2 介导的 ERK 激活诱导人毛囊真皮乳头细胞增殖。
DOI：
10.1016/j.yexcr.2012.05.003
复制
发表时间：
2012-08-15
影响因子：
3.7
通讯作者：
Zheng, Min
中科院分区：
文献类型：
--
作者：
Li, Wei;Man, Xiao-Yong;Zheng, Min
血管内皮生长因子（VEGF）是生理和病理性血管生成的最强调节因子之一。VEGF受体2（VEGFR-2）是VEGF的主要受体，被认为介导VEGF的主要功能作用。在此之前，我们已经在人毛囊中定位了VEGF和VEGFR-2。本研究进一步明确了VEGFR-2在人毛囊毛乳头（DP）细胞上的表达及其作用。分别采用逆转录-聚合酶链反应（RT-PCR）和Western印迹分析检测DP细胞上VEGFR-2的表达，并通过免疫荧光法确定VEGFR-2的定位。通过MU测定和特异性抑制剂分析VEGF对DP细胞的作用。最后，通过Western blot研究VEGF在信号通路中的作用。RT-PCR和Western blot分析证实DP细胞表达VEGFR-2。VEGFR-2的免疫染色在体外培养的人DP细胞上显示出强信号。外源性VEGF（165）以剂量依赖性方式刺激DP细胞增殖。此外，该刺激被VEGFR-2中和抗体（MAB 3571）和ERK抑制剂（PD 98059）阻断。VEGF（165）诱导的ERK 1/2磷酸化被MAB 3571和PD 98059消除，而p38、JNK和AKT的磷酸化不被VEGF（165）改变。总之，VEGFR-2在原代人毛囊DP细胞上表达，并且VEGF通过VEGFR-2/ERK途径而不是p38、JNK或AKT信号传导诱导DP细胞增殖。(C)2012 Elsevier Inc. All rights reserved.
Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MU assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF(165) stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF(165)-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF(165). Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. (C) 2012 Elsevier Inc. All rights reserved.