聚肌胞苷酸刺激的上皮细胞对成纤维细胞活化的影响及EMMPRIN的作用  

Effects of epithelial cells treated with poly(I:C) on activation of fibroblasts and roles of EMMPRIN

作　　者：陈兴无[1] 左蓓[1] 张新红[1] 

机构地区：[1]皖南医学院弋矶山医院呼吸内科,安徽芜湖241001

出　　处：《中国病理生理杂志》2012年第12期2197-2204,共8页Chinese Journal of Pathophysiology

基　　金：弋矶山医院引进人才专项科研基金资助项目(No.YR201012)

摘　　要：目的:探讨聚肌胞苷酸[poly(I:C)]作用上皮细胞后对气道成纤维细胞增殖和转分化的影响及细胞外基质金属蛋白酶诱导因子(EMMPRIN)的作用。方法:以poly(I:C)作用于人肺泡上皮细胞,将细胞上清刺激人气道成纤维细胞或种植在胶原凝胶中的成纤维细胞,观察后者增殖、α-平滑肌肌动蛋白(α-SMA)和EMM-PRIN表达及凝胶收缩;以EMMPRIN刺激成纤维细胞,检测细胞增殖、α-SMA表达及MMP-2、-9活性水平;应用p38 MAPK和ERK1/2抑制剂,观察对α-SMA表达及EMMPRIN分泌的影响。结果:Poly(I:C)作用的上皮细胞上清诱导成纤维细胞增殖、α-SMA和EMMPRIN表达及凝胶收缩;EMMPRIN剂量依赖性增强细胞增殖、α-SMA表达及MMP-2、-9活性;poly(I:C)作用的上皮细胞上清激活成纤维细胞p38 MAPK和ERK1/2信号通路,两者特异性阻断剂减弱成纤维细胞α-SMA和EMMPRIN表达。结论:Poly(I:C)作用上皮细胞后诱导成纤维细胞增殖、α-SMA表达和凝胶收缩,p38 MAPK和ERK1/2信号通路介导了上述过程,EMMPRIN是其中重要介质。AIM： To investigate the effects of epithelial cells treated with polyinosinic - polycytidylic acid [ pely （I ： C） ] on the proliferation, transdifferentiation and signaling mechanisms of airway fibroblasts. METHODS ： Human alveolar epithelial ceils were treated with poly（I：C）. The cell culture supernatants were used to stimulate the airway fibro- blasts or the fibroblasts growing in collagen gels. The proliferation of the fibroblasts, the expression of a - smooth muscle actin （ α - SMA） in the fibroblasts and the contractility of the collagen gels containing fibroblasts, as well as the expression of extracellular matrix metalloproteinase inducer （EMMPRIN） were observed. The proliferation of the fibroblasts and the expression levels of α - SMA, MMP - 2 and MMP - 9 in the fibroblasts stimulated with EMMPRIN were detected. The in- hibitors specific for p38 MAPK or ERK1/2 were used to explore the effects on α - SMA expression and EMMPRIN secre- tion. RESULTS ： The culture supernatants of the epithelial cells treated with poly （ I ： C） induced the proliferation, α - SMA expression and gel contraction as well as EMMPRIN secretion in the fibroblasts. EMMPRIN dose - dependently en- hanced fibroblast proliferation, α - SMA expression and activity of MMP - 2 and MMP - 9. The supernatants of epithelial cells treated with poly（I：C） activated p38 MAPK and ERK1/2 signaling in the fibroblasts, as the specific inhibitors of MAPK or ERK1/2 signaling attenuated the expression of α -SMA and EMMPRIN in the fibroblasts. CONCLUSION： Po- ly（I：C） induces fibroblast proliferation, α -SMA expression and gel contraction by affecting the process mediated by 1138 MAPK and ERK1/2 signaling pathways in epithelial cells. EMMPRIN may be the important media involved in this event.

关 键 词：聚肌胞苷酸 上皮细胞 成纤维细胞 Α-平滑肌肌动蛋白 细胞外基质金属蛋白酶诱导因子 

分 类 号：R562.25[医药卫生—呼吸系统]