Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice

Tetsuya Yokoyama, Toyoshi Yanagihara, Kunihiro Suzuki, Naoki Hamada, Kazuya Tsubouchi, Saiko Ogata-Suetsugu, Hironori Mikumo, Chika Ikeda-Harada, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi

Research output: Contribution to journalArticle

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Abstract

Background: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been clarified. We previously demonstrated DNA damage in murine bronchioles in the early stages of bleomycin-induced pulmonary fibrosis that subsequently extended to alveolar cells at the advanced stages of the disease. Club cells are progenitor cells for bronchioles and are known to play protective roles against lung inflammation and damage. The aim of the present study was to elucidate the role of club cells in the development of pulmonary fibrosis. Methods: C57BL/6 J mice received naphthalene intraperitoneally on day -2 to deplete club cells and were given intratracheal bleomycin or a vehicle on day 0. Lung tissues were obtained on days 1, 7, and 14, and bronchoalveolar lavage was performed on day 14. Bronchiolar epithelial cells sampled by laser capture microdissection were analyzed by gene expression microarray analysis on day 14. Results: Club cell depletion induced by naphthalene protected mice from bleomycin-induced lung injury and fibrosis. Bleomycin-triggered bronchiolar TGF-β1 expression was reduced. Gene expression microarray analysis revealed that genes associated with inflammatory response and chemokine activity were downregulated in the bleomycin-injured bronchiolar epithelium with club cell injury compared to that in bronchiolar epithelium without cell injury. Conclusions: Club cells are involved in the development of lung injury and fibrosis.

Original languageEnglish
Article number20
JournalJournal of Inflammation (United Kingdom)
Volume14
Issue number1
DOIs
Publication statusPublished - Sep 18 2017

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Bleomycin
Lung Injury
Fibrosis
Microarrays
Pulmonary Fibrosis
Gene expression
Microdissection
Bronchioles
Microarray Analysis
Chemokines
Epithelium
Epithelial Cells
Laser Capture Microdissection
Genes
Alveolar Epithelial Cells
Gene Expression
Tissue
Wounds and Injuries
Bronchoalveolar Lavage
Lasers

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

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Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice. / Yokoyama, Tetsuya; Yanagihara, Toyoshi; Suzuki, Kunihiro; Hamada, Naoki; Tsubouchi, Kazuya; Ogata-Suetsugu, Saiko; Mikumo, Hironori; Ikeda-Harada, Chika; Maeyama, Takashige; Kuwano, Kazuyoshi; Nakanishi, Yoichi.

In: Journal of Inflammation (United Kingdom), Vol. 14, No. 1, 20, 18.09.2017.

Research output: Contribution to journalArticle

Yokoyama, T, Yanagihara, T, Suzuki, K, Hamada, N, Tsubouchi, K, Ogata-Suetsugu, S, Mikumo, H, Ikeda-Harada, C, Maeyama, T, Kuwano, K & Nakanishi, Y 2017, 'Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice', Journal of Inflammation (United Kingdom), vol. 14, no. 1, 20. https://doi.org/10.1186/s12950-017-0168-1
Yokoyama, Tetsuya ; Yanagihara, Toyoshi ; Suzuki, Kunihiro ; Hamada, Naoki ; Tsubouchi, Kazuya ; Ogata-Suetsugu, Saiko ; Mikumo, Hironori ; Ikeda-Harada, Chika ; Maeyama, Takashige ; Kuwano, Kazuyoshi ; Nakanishi, Yoichi. / Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice. In: Journal of Inflammation (United Kingdom). 2017 ; Vol. 14, No. 1.
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