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

摘要

Aim To study the effects of extracellular signal-regulated kinasel/2 ( ERKI/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-ERKI/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- ERKI/2 significantlv increased and the expression levels of phosphor-ERKI/2 gradually decreased after 60,120 and 180 min. PD98059, a specific ERKI/2 inhibitor, significantly inhibited KGF-2-induced keratinocyte proliferation. Conclusion KGF2 activates ERKI/2 signaling pathway to enhance cell proliferation rate, which can be inhibited by ERK1/2inhibitor( PD98059 ). The effects of KGF-2 on keratinocyte wound healing may be related to ERKI/2signaling pathway-related role.%目的 观察角质细胞生长因子(keratinocyte growth factor-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;20 μmol·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.