降钙素基因相关肽通过ERK1/2信号通路对角质形成细胞增殖的影响

Calcitonin gene-related peptide triggers proliferation in HaCaT keratinocytes by ERK1/2 signaling pathway

目的:研究降钙素基因相关肽(CGRP)对角质形成细胞增殖活性的影响,并探讨其可能涉及的信号转导通路。方法:①胸腺嘧啶掺入法([3H]-TdR)观察CGRP诱导的角质形成细胞株HaCaT细胞增殖,及CGRP受体拮抗剂CGRP8-37、细胞外信号调节激酶ERK1/2特异性抑制剂PD98059对CGRP诱导的增殖活性的影响;②免疫印迹技术观察CGRP诱导后ERK1/2的磷酸化,及CGRP8-37、PD98059对ERK1/2磷酸化的影响。结果:①CGRP在一定范围内可剂量依赖性地诱导HaCaT细胞增殖,该作用可被CGRP8-37和PD98059阻断;②CGRP可时间依赖性地诱导HaCaT细胞ERK1/2的磷酸化,CGRP8-37和PD98059可减弱其作用。结论:CGRP可诱导HaCaT细胞增殖,CGRP受体及其相关的ERK1/2信号通路参与其调控机制。

AIM： To investigate the effect of calcitonin gene - related peptide （CGRP） on the proliferative potential of HaCaT keratinocytes and whether CGRPR and ERK1/2 pathway is involved in this progress, METHODS： [ 3H] - TdR test was used to estimate the CGRP - induced proliferative potential of HaCaT keratinocytes and the influence of CGRP8 -37 （CGRP receptor 1 antagonist） and PD98059 （ERK1/2 inhibitor） on this effect. Western blotting was used to test the activation of ERK1/2 pathway. RESULTS： Exposure of HaCaT keratinocytes to CGRP induced proliferation through the CGRP receptor and ERK1/2 pathway. CGRP 8 - 37 and PD98059 inhibited CGRP - induced proliferation of HaCaT keratinocytes. Phosphorylation of ERK1/2 was activated by CGRP in a time -dependent manner, which was inhibited by CGRP 8 -37 and PD98059. CONCLUSION： This study indicates that CGRP triggers the proliferation of HaCaT keratinocytes by CGRP receptor and ERK1/2 signaling pathway.