Histochemistry and Cell Biology

, Volume 129, Issue 4, pp 453–462 | Cite as

Dual-immunohistochemistry provides little evidence for epithelial–mesenchymal transition in pulmonary fibrosis

  • Mizuho Yamada
  • Kazuyoshi Kuwano
  • Takashige Maeyama
  • Naoki Hamada
  • Michihiro Yoshimi
  • Yoichi Nakanishi
  • Michael Kasper
Original Paper


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, T1α, or aquaporin 5, and a mesenchymal markers α-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 α-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.


Idiopathic pulmonary fibrosis Bleomycin epithelial–mesenchymal transition 



This work was supported by a Grant-in-Aid for Scientific Research (19390225) from the Ministry of Education, Science, and Culture of Japan.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Mizuho Yamada
    • 1
  • Kazuyoshi Kuwano
    • 2
  • Takashige Maeyama
    • 1
  • Naoki Hamada
    • 1
  • Michihiro Yoshimi
    • 1
  • Yoichi Nakanishi
    • 1
  • Michael Kasper
    • 3
  1. 1.Research Institute for Diseases of the Chest, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Division of Respiratory Diseases, Department of Internal MedicineJikei University School of MedicineTokyoJapan
  3. 3.Institute of AnatomyTechnical University of DresdenDresdenGermany

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