损伤上皮细胞ERK1/2通路活化并诱导上皮下成纤维细胞增殖

目的:探讨气道上皮损伤过程中ERK1/2信号通路的活化及其病理意义。方法:将原代培养的人支气管上皮细胞给予机械性损伤和(或)加入ERK1/2信号通路特异性抑制剂PD98059,采纳免疫组化、Western blotting或Zymog-raphy方法检测气道上皮细胞经机械损伤后ERK1/2的激活及MMP-2活性的变化;将损伤或加入MMP-2抑制剂的损伤上皮细胞上清刺激上皮下成纤维细胞,应用BrdU免疫组化检测成纤维细胞增殖的变化。结果:损伤诱导了上皮细胞ERK1/2信号通路的活化并促进活性MMP-2的释放,阻断ERK1/2信号通路减弱了损伤诱导的活性MMP-2水平;损伤上皮上清促进了成纤维细胞增殖,MMP-2抑制剂可阻断损伤上皮细胞上清的促增殖效应。结论:ERK1/2信号是损伤气道上皮高表达MMP-2进而诱导上皮下纤维化的一条重要信号通路。

ERK1/2 signal pathway activated in injured epithelial cells and promoted sub-epithelial fibroblasts proliferation

Objective:To explore the activation of extracellular signal-regulated kinase(ERK1/2) in injured airway epithelial cells and its pathological significance.Methods: Primary cultured human bronchial epithelial cells were treated by mechanical abrasion with or without adding the ERK1/2 specific inhibitor PD98059.The activation of ERK1/2 and activated MMP-9 levels in the mechanically injured airway epithelial cells were assessed by employing immunohistochemical staining,western blotting or zymography.Airway sub-epithelial fibroblasts were cultured with the supernatant from injured airway epithelial cells or supernatant from epithelial cells treated with injury by adding MMP-2 inhibitor while the proliferation of fibroblasts was valuated by BrdU.Results: The findings suggested that injury could induce the activation of ERK1/2 pathway in airway epithelial cells and promote releasing of activated MMP-2 from injured epithelial cells,and further ERK1/2 inhibitor abolished the induced MMP-2 activity by injury.Supernatant from injured airway epithelial cells enhanced the proliferation of airway fibroblasts compared with controls,while MMP-2 inhibitor attenuated the induced proliferation to a certain extent.Conclusion:ERK1/2 may be an important signal pathway which contributes to MMP-2 hyper-expression from injured airway epithelial cells and airway sub-epithelial fibrosis.