Institution of Drug Clinical Trial, Guangdong Second Provincial General Hospital, Guangzhou 510317, China.
Laboratory of Vascular Biology, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001 Hunan, China.
Mediators Inflamm. 2018 Jun 12;2018:2109352. doi: 10.1155/2018/2109352. eCollection 2018.
Calcitonin gene-related peptide (CGRP) has a potent protective action on the cardiovascular system; however, little is known about the role of CGRP in angiotensin II- (Ang II-) induced inflammation of vascular smooth muscle cells (VSMCs). This study is aimed at determining the anti-inflammatory effect of CGRP in Ang II-treated VSMCs and whether a disintegrin and metalloproteinase 17 (ADAM17) modulates this protective action. Small interference RNA (siRNA) and inhibitors of CGRP, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase 1/2 (ERK1/2) were adopted to investigate their effect on Ang II-induced inflammation in VSMCs. Here, we found that CGRP could inhibit inflammation and decrease ADAM17 expression and activation of EGFR and ERK1/2 in VSMCs stimulated with Ang II. Results of siRNA demonstrated that ADAM17 siRNA attenuated Ang II-induced inflammation and up-regulation of activities of EGFR and ERK1/2 in VSMCs. Furthermore, the EGFR-ERK1/2 pathway promoted Ang II-induced VSMC inflammation. In summary, these findings identify the anti-inflammatory effect of CGRP in VSMCs stimulated by Ang II and suggest that ADAM17 is involved in the protective effect of CGRP against Ang II-induced inflammation via the EGFR-ERK1/2 pathway in VSMCs.
降钙素基因相关肽（CGRP）对心血管系统具有强大的保护作用；然而，关于 CGRP 在血管平滑肌细胞（VSMCs）中血管紧张素 II （Ang II）诱导的炎症中的作用知之甚少。本研究旨在确定 CGRP 在 Ang II 处理的 VSMCs 中的抗炎作用，以及解整合素和金属蛋白酶 17（ADAM17）是否调节这种保护作用。采用小干扰 RNA（siRNA）和 CGRP、表皮生长因子受体（EGFR）和细胞外信号调节激酶 1/2（ERK1/2）的抑制剂来研究它们对 Ang II 诱导的 VSMCs 炎症的影响。在这里，我们发现 CGRP 可以抑制炎症，降低 Ang II 刺激的 VSMCs 中 ADAM17 的表达和 EGFR 和 ERK1/2 的激活。siRNA 的结果表明，ADAM17 siRNA 减弱了 Ang II 诱导的 VSMCs 炎症和 EGFR 和 ERK1/2 的活性上调。此外，EGFR-ERK1/2 通路促进了 Ang II 诱导的 VSMC 炎症。总之，这些发现确定了 CGRP 在 Ang II 刺激的 VSMCs 中的抗炎作用，并表明 ADAM17 通过 EGFR-ERK1/2 通路参与了 CGRP 对 Ang II 诱导的炎症的保护作用。
