Effects of ERK Signaling Pathway on Cell Cycle in Airway Smooth Muscle Cells of Chronic Asthmatic Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

BAI Jing , LIU Xiansheng , XU Yongjian , XIE Ming , NI WangCorresponding AuthorLIU Xiansheng

Department of Respiratory Medicine，Tongji Hospital Affiliated to Tongji Medical College，Huazhong University of Science and Technology. Wuhan，Hubei，430030，China;

Corresponding author：

Keywords：

Extracellular signal regulated kinase; Airway; Smooth muscle cell; Cell Cycle

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Objective To investigate the effects of extracellular signal regulated kinase ( ERK)signaling pathway on cell cycle of airway smooth muscle cells( ASMCs) in asthmatic rats. Methods Thirty Wistar rats were randomly assigned to a control group and an asthma group( 15 rats in each group) . Asthma model was established by ovalbumim sensitization and challenge. ASMC were isolated and cultured in vitro. The ASMCs from the asthmatic rats were treated with ERK activator epidermal growth factor ( EGF)
and inhibitor PD98059, respectively. The expressions of cyclin D1 and CDK2 in ASMCs were detected by immunocytochemical staining. The expressions of ERK1 /2 and p-ERK1 /2 protein were observed by western blotting for measurement of ERK activation rate. Results Compared with the control group[ 54. 17 ±6. 11,61. 04 ±4. 09, ( 49. 91 ±3. 26) % , respectively] , the expressions of cyclin D1 protein and CDK2 protein,and the rate of ERK activation of ASMCs from the asthmatic rats significantly increased[ 76. 15 ±4. 88,92. 30 ±7. 95, ( 82. 37 ±5. 78) % , respectively] ( P lt; 0. 05) . Furthermore, compared with those before treatment, the expression of cyclin D1 and CDK2, and the rate of ERK activation of ASMCs significantly decreased after treatment with PD98059 [ 58. 78 ±4. 60, 69. 15 ±5. 83, ( 54. 01 ±4. 12) % , respectively]
( P lt; 0. 05) , and significantly increased after treatment with EGF[ 119. 28 ±8. 14, 134. 77 ±9. 26, ( 91. 57 ±5. 32) %, respectively] ( P lt;0. 05) . Conclusion ERK1/ 2 participates in proliferation regulation of ASMCs in asthma by enhancing the expressions of cyclin D1 and CDK2, which promotes quiescent cells into S phase.

Citation： BAI Jing,LIU Xiansheng,XU Yongjian,XIE Ming,NI WangCorresponding AuthorLIU Xiansheng,Emailliuxianshengtjh.tjmu.edu.cn. Effects of ERK Signaling Pathway on Cell Cycle in Airway Smooth Muscle Cells of Chronic Asthmatic Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(1): 23-27. doi: Copy

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1. Kumar RK.Understanding airway wall remodeling in asthma: a basis for improvements in therapy? Pharmacol Ther,2001,91:93-104.
2. 白晶,刘先胜,徐永健,等.细胞外信号调节激酶活化在慢性支气管哮喘大鼠气道平滑肌细胞增殖中的作用.生理学报,2007,59,311-318.
3. Kumar RK,Herbert C,Thomas PS,et al.Inhibition of inflammation and remodeling by roflumilast and dexamethasone in murine chronic asthma. J Pharmacol Exp Ther,2003,307:349-355.
4. Salmon M,Walsh DA,Koto H,et al.Repeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synthesis and remodelling. Eur Respir J,1999,14:633-641.
5. 白晶,刘先胜,徐永健,等.ERK反义寡核苷酸对支气管哮喘大鼠气道平滑肌细胞增殖和凋亡的影响.中华内科杂志,2007, 46:497-499.
6. Xiong W, Pestell RG,Watanabe G,et al.Cyclin D1 is required for S phase traversal in bovine tracheal myocytes. Ann J Physiol,1997,272: L1205-L1210.
7. Amrani Y,Tliba O,Choubey D,et al.IFN-gamma inhibits human airway smooth muscle cell proliferation by modulating the E2F-1/Rb pathway. Am J Physiol Lung Cell Mol Physiol,2003,284:L1063-1071.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of ERK Signaling Pathway on Cell Cycle in Airway Smooth Muscle Cells of Chronic Asthmatic Rats

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