Zhou Yong, Zhang Min, Sun Guo-Ying, Liu Yong-Ping, Ran Wen-Zhuo, Peng Li, Guan Cha-Xiang
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.
Regul Pept. 2013 Jun 10;184:22-9. doi: 10.1016/j.regpep.2013.03.020. Epub 2013 Mar 15.
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendritic cell function, stimulate proliferation of alveolar epithelial cells and mediate lung injury in mice. In this study, we investigated the effect of CGRP on the wound healing of human bronchial epithelial cells (HBECs) in vitro. The results showed that CGRP accelerated the recovery of wound area of monolayer HBECs in a dose-dependent manner. CGRP inhibited the lipopolysaccharide-induced apoptosis in HBECs. The percentage of S phase and G2/M phase was increased in HBECs after CGRP treatment. CGRP upregulated the expression of Ki67 in a dose-dependent manner. Some pathway inhibitors were used to investigate the signal pathway in which CGRP was involved. We found out that PKC pathway inhibitor (H-7) and MAPK pathway inhibitor (PD98059) could partially attenuate the effect of CGRP, which indicated that CGRP might promote the wound healing of HBECs via PKC and/or MAPK dependent pathway by accelerating migration and proliferation, and inhibiting apoptosis.
降钙素基因相关肽(CGRP)是一种由降钙素基因衍生而来的含37个氨基酸的神经肽。CGRP广泛分布于中枢和外周神经系统。在肺中,CGRP可调节树突状细胞功能,刺激肺泡上皮细胞增殖并介导小鼠肺损伤。在本研究中,我们在体外研究了CGRP对人支气管上皮细胞(HBECs)伤口愈合的影响。结果表明,CGRP以剂量依赖的方式加速了单层HBECs伤口面积的恢复。CGRP抑制了脂多糖诱导的HBECs凋亡。CGRP处理后,HBECs中S期和G2/M期的百分比增加。CGRP以剂量依赖的方式上调了Ki67的表达。使用一些通路抑制剂来研究CGRP所涉及的信号通路。我们发现蛋白激酶C(PKC)通路抑制剂(H-7)和丝裂原活化蛋白激酶(MAPK)通路抑制剂(PD98059)可部分减弱CGRP的作用,这表明CGRP可能通过PKC和/或MAPK依赖性通路,通过加速迁移和增殖以及抑制凋亡来促进HBECs的伤口愈合。