特发性肺间质纤维化中TGF-β1诱导上皮-间充质细胞转化的研究

Expression of TGF-β1 in idiopathic pulmonary fibrosis and its pathological significance

关键词:  特发性肺间质纤维化  上皮-间充质细胞转化  转化生长因子-β1

Key words:  idiopathic pulmonary fibrosis  epithelial-mesenchymal transition  tansforming growth factor-β1

摘要:

目的探讨转化生长因子-β1(tansforming growth factor-β1,TGF-β1)在特发性肺间质纤维化(idiopathicpulmonary fibrosis,IPF)中上皮-间充质细胞转化(epithelial-mesenchymal transition,EM T)的作用和机制。方法选择临床-影像-病理诊断的IPF患者25例肺石蜡组织制作组织芯片,应用免疫组化方法检测病灶组织中TGF-β1和β连环蛋白(β-catenin),间质标记物α-SMA、Desmin、Vim和上皮标记物E-cadherin及CK7的分布及表达情况。结果TGF-β1主要分布于肌纤维母细胞、Ⅱ型肺泡上皮细胞和巨噬细胞,且其在成纤维细胞灶(fibroblast foci,FF)区域内各种细胞中的表达明显高于无FF区域(P<0.01);与无FF区域相比,β-catenin和E-cadherin在有FF区域增生的Ⅱ型肺泡上皮细胞膜表达明显减弱(P<0.01),而胞浆的表达明显增加(P<0.01);同时发现有FF区域Ⅱ型肺泡上皮细胞表达间质标记物Vim,但未发现α-SMA的表达,而无FF区域两者均无表达。结论 TGF-β1和β-catenin有可能通过相互交叉作用诱导Ⅱ型肺泡上皮细胞发生EMT,从而参与肺间质纤维化的发生。

Abstract:

Objective To investigate the expression of TGF-β1 in idiopathic pulmonary fibrosis（IPF） and its pathological significance.Methods Twenty-five patients with IPF were enrolled in the study.The distribution and expression of TGF-β1,β-catenin,α-SMA,Desmin,Vim,E-cadherin and CK7 were examined by immunohistochemical staining on tissue microarray slides.Results TGF-β1 was mainly distributed in myofibroblasts,type Ⅱ alveolar epithelial cells and macrophages.Its expression was significantly stronger in fibroblast foci（FF） area than that in non-FF area（P＜0.01）.Compared to non-FF area,the membranous expression of β-catenin and E-cadherin on type Ⅱ alveolar epithelial cells in FF area was significantly weaker（P＜0.01）,while cytoplasmic expression was significantly stronger（P＜0.01）.Type Ⅱ alveolar epithelial cells in FF area expressed Vim,not α-SMA;meanwhile neither of them were expressed in non-FF area.Conclusion TGF-β1 is strongly expressed in lung tissue of IPF patients,indicating that its interaction with β-catenin might be involved in pulmonary fibrosis through epithelial-mesenchymal transition of alveolar type Ⅱ epithelial cells.