Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice
Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large...
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KeAi Communications Co., Ltd.
2017-12-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304217300636 |
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| author | Danyi Peng Daozhu Si Rong Zhang Jiang Liu Hao Gou Yunqiu Xia Daiyin Tian Jihong Dai Ke Yang Enmei Liu Yujun Shi Q. Richard Lu Lin Zou Zhou Fu |
| author_facet | Danyi Peng Daozhu Si Rong Zhang Jiang Liu Hao Gou Yunqiu Xia Daiyin Tian Jihong Dai Ke Yang Enmei Liu Yujun Shi Q. Richard Lu Lin Zou Zhou Fu |
| author_sort | Danyi Peng |
| collection | DOAJ |
| description | Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ) model, as well as a new SMARCA4-deleted alveolar type II (ATII)-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF. |
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| last_indexed | 2025-03-22T04:36:58Z |
| publishDate | 2017-12-01 |
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| series | Genes and Diseases |
| spelling | doaj.art-0415d65da66f421da8fdadf1cd0999952024-04-28T00:23:51ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422017-12-014420421410.1016/j.gendis.2017.10.001Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in miceDanyi Peng0Daozhu Si1Rong Zhang2Jiang Liu3Hao Gou4Yunqiu Xia5Daiyin Tian6Jihong Dai7Ke Yang8Enmei Liu9Yujun Shi10Q. Richard Lu11Lin Zou12Zhou Fu13Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaLaboratory of Pathology, West China Hospital, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu 610041, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaPediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, ChinaAlveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ) model, as well as a new SMARCA4-deleted alveolar type II (ATII)-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.http://www.sciencedirect.com/science/article/pii/S2352304217300636Cell proliferationPulmonary fibrosisSMARCA4Transgenic miceType II alveolar epithelial cells |
| spellingShingle | Danyi Peng Daozhu Si Rong Zhang Jiang Liu Hao Gou Yunqiu Xia Daiyin Tian Jihong Dai Ke Yang Enmei Liu Yujun Shi Q. Richard Lu Lin Zou Zhou Fu Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice Genes and Diseases Cell proliferation Pulmonary fibrosis SMARCA4 Transgenic mice Type II alveolar epithelial cells |
| title | Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice |
| title_full | Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice |
| title_fullStr | Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice |
| title_full_unstemmed | Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice |
| title_short | Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice |
| title_sort | deletion of smarca4 impairs alveolar epithelial type ii cells proliferation and aggravates pulmonary fibrosis in mice |
| topic | Cell proliferation Pulmonary fibrosis SMARCA4 Transgenic mice Type II alveolar epithelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S2352304217300636 |
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