Effects of airway epithelium injury on the transdifferentiation of sub-epithelial fibroblasts and its role in the development of airway hyperresponsiveness in asthma
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF TUBERCULOSIS AND RESPIRATORY DISEASES
- Issue:
- 10
- DOI:
- 10.3760/j:issn:1001-0939.2005.10.012
- Key Word:
- 气道上皮;上皮下成纤维细胞;α平滑肌肌动蛋白;内皮素1;转化生长因子β1;丝裂原活化蛋白激酶
Abstract： 目的探讨损伤气道上皮对上皮下成纤维细胞活化、转分化为肌纤维母细胞的影响及其在支气管哮喘(简称哮喘)气道高反应中的地位.方法原代培养的人气道上皮下成纤维细胞与经脂多糖 (LPS)处理后给予机械划伤的人气道上皮细胞(16HBE)共培养,分别加入内皮素(ET)受体A拮抗剂BQ123、转化生长因子β1(TGF-β1)中和抗体及丝裂原活化蛋白激酶(MAPKs)信号通路特异性抑制剂,应用免疫组化、免疫印迹以及5-溴-2'-脱氧尿苷(BrdU)掺入等方法,检测上皮下成纤维细胞α平滑肌肌动蛋白(α-SMA)的表达与细胞增殖情况;将细胞转染反义内皮素转换酶(anti-ECE)mRNA表达载体并运用酶谱分析法, 研究ET-1与基质金属蛋白酶(MMPs)的相互作用.结果损伤上皮诱导并增强了上皮下成纤维细胞α-SMA表达及细胞增殖,同时诱导了上皮下成纤维细胞p38丝裂原活化蛋白激酶(p38MAPK)及细胞外信号调节激酶(ERK1/2)信号通路的活化;BQ123、TGF-β1中和抗体及p38 MAPK、ERK1/2抑制剂均分别抑制或部分抑制了α-SMA的表达.与对照(转染空载体)及转染anti-ECE mRNA表达载体上皮细胞比较, 转染空载体的上皮细胞损伤后上清液中ET-1分泌[机械划伤+LPS刺激的pEGFPN2转染16HBE组为(15.00±0.86) pg/ml;机械划伤+LPS刺激的anti-ECE转染16HBE组为(7.57±0.94) pg/ml]增加(P均<0.01).结论损伤上皮通过释放ET-1和(或)TGF-β1诱导了上皮下成纤维细胞向肌纤维母细胞转分化并促进了细胞的增殖,这一过程涉及了MAPKs家族的p38 MAPK与ERK1/2信号通路的激活.
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