ERK1/2信号通路在角质细胞生长因子-2诱导角膜基质细胞增殖中的作用  

Role of ERK-1/2 signaling pathway in keratinacyte growth factor-2 stimulating human keratinocyte proliferation

作　　者：高丽昌[1,2,3] 李婷婷[1,2,3] 李富勇[2] 唐禄[2] 李海燕[1] 王晓杰[2,1] 李校堃[2,1] 

机构地区：[1]吉林农业大学生物反应器与药物开发教育部工程研究中心,吉林长春130021 [2]温州医学院药学院,浙江温州325035 [3]吉林农业大学生命科学学院,吉林长春130021

出　　处：《中国药理学通报》2011年第10期1405-1408,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81070714);"重大新药创制"科技重大专项资助项目(No2008ZX09101-057);吉林省科技厅资助项目(No20100951);长春市科技计划资助项目(No08YJ45);长春市企业科技特派员行动计划资助项目(No09KT03)

摘　　要：目的观察角质细胞生长因子(keratinocyte growthfactor-2,KGF-2)对角膜基质细胞的增殖作用及ERK1/2信号在角膜基质细胞增殖中的调控作用,探讨KGF-2对角膜基质细胞增殖的可能机制。方法体外培养角膜基质细胞,MTT法检测细胞增殖,Western blot检测磷酸化ERK1/2表达水平。结果 KGF-2在1～100 mg·L-1对角膜基质细胞有明显的促进增殖作用且呈现剂量-效应关系;100 mg·L-1 KGF-2处理角膜基质细胞,5、15、30 min后ERK1/2磷酸化表达水平明显升高,60、90、120、180 min后ERK1/2磷酸化表达水平逐渐减弱;20μmol.L-1 ERK1/2抑制剂PD98059可抑制KGF-2对角膜基质细胞的促增殖作用。结论 KGF-2激活ERK1/2信号通路,提高细胞增殖率,可被抑制剂PD98059阻断;ERK1/2信号通路调控角膜基质细胞的增殖,在角膜基质细胞损伤中发挥作用。Aim To study the effects of extracellular signal-regulated kinase1/2（ERK1/2） on the Keratinocyte Growth Factor-2（KGF-2）-induced proliferation in human keratinocyte.Method Human keratinocytes were cultured in vitro.Cell proliferation was detected by MTT.Western-blot was used to detect the expression levels of phospho-ERK1/2.Result KGF-2（1~100 mg·L-1） significantly increased keratinocytes proliferation in a dose-dependent manner.Keratinocytes were treated with 100 mg·L-1 KGF-2 for 5min,15min and 30min,the expression levels of phosphor-ERK1/2 significantly increased and the expression levels of phosphor-ERK1/2 gradually decreased after 60,120 and 180 min.PD98059,a specific ERK1/2 inhibitor,significantly inhibited KGF-2-induced keratinocyte proliferation.Conclusion KGF-2 activates ERK1/2 signaling pathway to enhance cell proliferation rate,which can be inhibited by ERK1/2 inhibitor（PD98059）.The effects of KGF-2 on keratinocyte wound healing may be related to ERK1/2signaling pathway-related role.

关 键 词：角质细胞生长因子-2 ERK1/2 PERK1/2 信号通路 角膜基质细胞 细胞增殖 

分 类 号：R322.91[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]