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Investigation and regulation of molecular mechanisms of epithelial mesenchymal transition in pulmonary fibrosis

肺纤维化上皮间质转化分子机制的研究与调控

基本信息

批准号：
17590793
负责人：
KUWANO Kazuyoshi
金额：
$ 2.24万
依托单位：
KYUSHU UNIVERCITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590793/
关键词：
pulmonary fibrosis lung injury EMT apoptosis bleomycin TGF-beta 特発性間質性肺炎特発性肺線維症

项目摘要

Epithelial-mesenchymal transition (EMT) has been considered to be involved in organ fibrogenesis. However, there is few direct evidence of this process in the pathophysiology of pulmonary fibrosis in vivo. Therefore, we tried to verify the involvement of this process in the development of pulmonary fibrosis. Since the co-expressions of epithelial and mesenchymal markers are thought to be a marker of EMT, we performed dual immunohistochemistry to assess the co-expressions of these proteins in lung tissues from bleomycin-induced pulmonary fibrosis in mice, and from patients with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Double positive cells for epithelial markers including E-cadherin, CD44v10,T1α, or aquaporin 5,and a mesenchymal marker α-smooth muscle actin were rarely found in bleomycin-induced pulmonary fibrosis in mice. Double positive cells for E-cadherin, ICAM-1,LEA, CD44v9,or SP-A and a-smooth muscle actin were not found in lung tissues from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. In contrast to few incidence of EMT, we occasionally found intermediate cells which have characteristics of type I and type II or bronchiolar epithelial cells. These results suggest that EMT may be present in pulmonary fibrosis, but have minor role in the pathophysiology of pulmonary fibrosis.

上皮间质转化（EMT）被认为参与器官纤维发生。然而，在体内肺纤维化的病理生理学中，很少有直接证据表明这一过程。因此，我们试图验证这一过程是否参与肺纤维化的发展。由于上皮和间质标记物的共表达被认为是 EMT 的标记物，因此我们进行了双重免疫组织化学来评估这些蛋白质在博来霉素诱导的小鼠肺纤维化以及特发性肺纤维化和非特异性间质性肺炎患者的肺组织中的共表达。在博莱霉素诱导的小鼠肺纤维化中，很少发现上皮标记物（包括 E-钙粘蛋白、CD44v10、T1α 或水通道蛋白 5）和间充质标记物 α-平滑肌肌动蛋白双阳性细胞。特发性肺纤维化和非特异性间质性肺炎肺组织中未发现E-钙粘蛋白、ICAM-1、LEA、CD44v9或SP-A和α-平滑肌肌动蛋白双阳性细胞。与很少发生的EMT相反，我们偶尔发现具有I型和II型或细支气管上皮细胞特征的中间细胞。这些结果表明EMT可能存在于肺纤维化中，但在肺纤维化的病理生理学中作用较小。