Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice
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 a...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-09-01
|
| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12950-017-0168-1 |
| _version_ | 1828920132288643072 |
|---|---|
| author | Tetsuya Yokoyama Toyoshi Yanagihara Kunihiro Suzuki Naoki Hamada Kazuya Tsubouchi Saiko Ogata-Suetsugu Hironori Mikumo Chika Ikeda-Harada Takashige Maeyama Kazuyoshi Kuwano Yoichi Nakanishi |
| author_facet | Tetsuya Yokoyama Toyoshi Yanagihara Kunihiro Suzuki Naoki Hamada Kazuya Tsubouchi Saiko Ogata-Suetsugu Hironori Mikumo Chika Ikeda-Harada Takashige Maeyama Kazuyoshi Kuwano Yoichi Nakanishi |
| author_sort | Tetsuya Yokoyama |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T21:40:06Z |
| format | Article |
| id | doaj.art-bb92124a46014cd08eedf27a2e9b2b11 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-12-13T21:40:06Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-bb92124a46014cd08eedf27a2e9b2b112022-12-21T23:30:34ZengBMCJournal of Inflammation1476-92552017-09-011411910.1186/s12950-017-0168-1Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in miceTetsuya Yokoyama0Toyoshi Yanagihara1Kunihiro Suzuki2Naoki Hamada3Kazuya Tsubouchi4Saiko Ogata-Suetsugu5Hironori Mikumo6Chika Ikeda-Harada7Takashige Maeyama8Kazuyoshi Kuwano9Yoichi Nakanishi10Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of MedicineResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of MedicineResearch Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu UniversityAbstract 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.http://link.springer.com/article/10.1186/s12950-017-0168-1Club cellLung injuryLung fibrosis |
| spellingShingle | Tetsuya Yokoyama Toyoshi Yanagihara Kunihiro Suzuki Naoki Hamada Kazuya Tsubouchi Saiko Ogata-Suetsugu Hironori Mikumo Chika Ikeda-Harada Takashige Maeyama Kazuyoshi Kuwano Yoichi Nakanishi Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice Journal of Inflammation Club cell Lung injury Lung fibrosis |
| title | Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice |
| title_full | Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice |
| title_fullStr | Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice |
| title_full_unstemmed | Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice |
| title_short | Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice |
| title_sort | depletion of club cells attenuates bleomycin induced lung injury and fibrosis in mice |
| topic | Club cell Lung injury Lung fibrosis |
| url | http://link.springer.com/article/10.1186/s12950-017-0168-1 |
| work_keys_str_mv | AT tetsuyayokoyama depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT toyoshiyanagihara depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT kunihirosuzuki depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT naokihamada depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT kazuyatsubouchi depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT saikoogatasuetsugu depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT hironorimikumo depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT chikaikedaharada depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT takashigemaeyama depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT kazuyoshikuwano depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice AT yoichinakanishi depletionofclubcellsattenuatesbleomycininducedlunginjuryandfibrosisinmice |