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

Journal of Inflammation

Research

Kazuya Tsubouchi¹  Kazuyoshi Kuwano¹  Yoichi Nakanishi²  Toyoshi Yanagihara²  Chika Ikeda-Harada²  Naoki Hamada²  Hironori Mikumo²  Tetsuya Yokoyama²  Saiko Ogata-Suetsugu²  Kunihiro Suzuki²  Takashige Maeyama² 

[1] Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan;Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;

关键词: Club cell;    Lung injury;    Lung fibrosis;   

DOI  :  10.1186/s12950-017-0168-1

 received in 2017-07-18, accepted in 2017-09-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsC57BL/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.ResultsClub 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.ConclusionsClub cells are involved in the development of lung injury and fibrosis.

【 授权许可】

CC BY   
© The Author(s). 2017