标题：Role of the extracellular signal-regulated kinase 1/2 signaling pathway in the process of thrombin-promoting airway remodeling in ovalbumin-allergic rats
作者：Bi, Meirong; Guo, Aili; Zhao, Hongyang; Sun, Xuewu; Chen, Qiang; Yu, Li; Shi, Wei; Wang, Yan; Shen, Guohong; Wang, Xueying; Zhao, 更多 作者机构：[Bi, Meirong; Guo, Aili; Zhao, Hongyang; Shen, Guohong; Wang, Xueying; Zhao, Yingchun; Zhang, Nan; Xu, Mi; Qin, Mingming; Zhu, Weiwei] Shandong Univ, 更多
通讯作者地址：[Zhu, WW]Shandong Univ, Jinan Cent Hosp, Dept Pediat, 105 Jiefang Rd, Jinan, Shandong, Peoples R China.
来源：IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
关键词：Airway remodeling; asthma; PD98059; pERK1/2; rat; thrombin
摘要：Context: Although it is recognized that thrombin plays a key role in airway remodeling during chronic asthma. In a previous study, we have proved that thrombin promotes airway remodeling via PAR-1 in OVA-allergic rats, but little is known about intracellular signaling pathway involved in the event.; Objective: In this study, we intend to explore the impact of pERK1/2 signaling pathway on the process of thrombin-induced airway remodeling in OVA-allergic rats. Materials and methods: A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06, and pERK1/2 inhibitor PD98059 varied for different groups. The expression of pERK1/2 was analyzed by western blot and RT-PCR. Secretion of TGF-beta 1 and IL-6 was detected by ELISA.; Results: The expression of pERK1/2 was higher in the airway of asthmatic rats than those of normal rats, and was significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was enhanced by thrombin but weakened by pERK1/2 inhibitor. Expression of growth factors and IL-6 in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and pERK1/2 inhibitor treatment.; Conclusion: These results suggest that ERK1/2 signaling pathway may play an important role in the process of thrombin-promoting airway remodeling in OVA-allergic rats, and pERK1/2 inhibitor effectively inhibits the process.