Dual-immunohistochemistry provides little evidence for epithelial-mesenchymal transition in pulmonary fibrosis
Dual-immunohistochemistry provides little evidence for epithelial-mesenchymal transition in pulmonary fibrosis
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DOI：
10.1007/s00418-008-0388-9
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发表时间：
2008-04-01
影响因子：
2.3
通讯作者：
Kasper, Michael
中科院分区：
文献类型：
--
作者：
Yamada, Mizuho;Kuwano, Kazuyoshi;Kasper, Michael
上皮-间质转化（EMT）被认为参与器官纤维化。然而，在体内肺纤维化的病理生理学中很少有这一过程的直接证据。因此，我们试图证实这一过程参与肺纤维化的发展。由于上皮和间充质标志物的共表达被认为是EMT的标志物，我们进行了双重免疫组织化学，以评估这些蛋白质在博莱霉素诱导的肺纤维化小鼠肺组织中的共表达，以及特发性肺纤维化和非特异性间质性肺炎患者。在博莱霉素诱导的小鼠肺纤维化中未发现上皮标志物（包括E-钙粘蛋白、T1 α或水通道蛋白5）和间充质标志物α-平滑肌肌动蛋白或波形蛋白的双阳性细胞。在正常肺组织、特发性肺纤维化和非特异性间质性肺炎肺组织中均未发现E-cadherin、ICAM-1、莱亚、CD 44 v9、SP-A和α-平滑肌肌动蛋白或波形蛋白的双阳性细胞。这些结果至少提供了两种可能性。一是在IPF或博莱霉素诱导的小鼠肺纤维化中不发生EMT。另一个是EMT可能发生在肺纤维化中，但在此转变期间，细胞表达可检测水平的上皮和间充质标志物的时间太短，无法通过双重免疫组化检测到。
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-immuunohistochemistry 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, T1 alpha, or aquaporin 5, and a mesenchymal markers alpha-smooth muscle actin or vimentin were not found in bleomycin-induced pulmonary fibrosis in mice. Double positive cells for E-cadherin, ICAM-1, LEA, CD44v9, or SP-A and alpha-smooth muscle actin or vimentin were not found in lung tissues from normal lung parenchyma, idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. These results offer at least two possibilities. One is that EMT does not occur in IPF or bleomycin-induced pulmonary fibrosis in mice. Another is that EMT may occur in pulmonary fibrosis but the time during this transition in which cells express detectable levels of epithelial and mesenchymal markers is too small to be detected by double immunohistochemistry.