Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis
Abstract Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by fibroblast proliferation, extensive extracellular matrix and collagen deposition, accompanied by inflammatory damage, ultimately leading to death due to respiratory failure. Endoplasmic reticulum (ER) stress in...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-024-03016-5 |
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| author | Zhiheng Sun Wanyu He Huiwen Meng Zhihua Ji Junxing Qu Guoying Yu |
| author_facet | Zhiheng Sun Wanyu He Huiwen Meng Zhihua Ji Junxing Qu Guoying Yu |
| author_sort | Zhiheng Sun |
| collection | DOAJ |
| description | Abstract Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by fibroblast proliferation, extensive extracellular matrix and collagen deposition, accompanied by inflammatory damage, ultimately leading to death due to respiratory failure. Endoplasmic reticulum (ER) stress in pulmonary fibrotic tissue is indeed recognized as a significant factor exacerbating PF development. Emerging evidences indicated a potential association between ER stress induced by lactate and cellular apoptosis in PF. However, the mechanisms in this process need further elucidation. In this paper, pulmonary fibrosis model was induced by bleomycin (BLM) intratracheally in mice. In the cellular model, type II epithelial cells were treated by lactate and TGF-β to detect ER stress and apoptosis markers. Lactate could promote ER stress response and apoptosis. Mechanically, lactate activated Caspase-12 via ATF4-Chop axis to induce cell apoptosis and promote fibrosis. ER stress inhibitor could effectively suppress alveolar epithelial cells apoptosis and pulmonary fibrosis. We concluded that pro-fibrotic properties of lactate are associated with alveolar epithelial cells apoptosis by causing ER stress and thus provide new potential therapeutic targets for pulmonary fibrosis. |
| format | Article |
| id | doaj-art-3ddf18c53a2649aeabaf0da96018f659 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-3ddf18c53a2649aeabaf0da96018f6592024-11-10T12:40:07ZengBMCRespiratory Research1465-993X2024-11-0125111610.1186/s12931-024-03016-5Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosisZhiheng Sun0Wanyu He1Huiwen Meng2Zhihua Ji3Junxing Qu4Guoying Yu5College of Life Science, Institute of Biomedical Science, Henan Normal UniversityCollege of Life Science, Institute of Biomedical Science, Henan Normal UniversityCollege of Life Science, Institute of Biomedical Science, Henan Normal UniversityCollege of Life Science, Institute of Biomedical Science, Henan Normal UniversityInstitutes of Health Central Plains, Xinxiang Medical UniversityCollege of Life Science, Institute of Biomedical Science, Henan Normal UniversityAbstract Pulmonary fibrosis (PF) is a chronic, progressive lung disease characterized by fibroblast proliferation, extensive extracellular matrix and collagen deposition, accompanied by inflammatory damage, ultimately leading to death due to respiratory failure. Endoplasmic reticulum (ER) stress in pulmonary fibrotic tissue is indeed recognized as a significant factor exacerbating PF development. Emerging evidences indicated a potential association between ER stress induced by lactate and cellular apoptosis in PF. However, the mechanisms in this process need further elucidation. In this paper, pulmonary fibrosis model was induced by bleomycin (BLM) intratracheally in mice. In the cellular model, type II epithelial cells were treated by lactate and TGF-β to detect ER stress and apoptosis markers. Lactate could promote ER stress response and apoptosis. Mechanically, lactate activated Caspase-12 via ATF4-Chop axis to induce cell apoptosis and promote fibrosis. ER stress inhibitor could effectively suppress alveolar epithelial cells apoptosis and pulmonary fibrosis. We concluded that pro-fibrotic properties of lactate are associated with alveolar epithelial cells apoptosis by causing ER stress and thus provide new potential therapeutic targets for pulmonary fibrosis.https://doi.org/10.1186/s12931-024-03016-5Pulmonary fibrosisLactateEndoplasmic reticulum stressCaspase-12Alveolar epithelial cellsApoptosis |
| spellingShingle | Zhiheng Sun Wanyu He Huiwen Meng Zhihua Ji Junxing Qu Guoying Yu Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis Respiratory Research Pulmonary fibrosis Lactate Endoplasmic reticulum stress Caspase-12 Alveolar epithelial cells Apoptosis |
| title | Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis |
| title_full | Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis |
| title_fullStr | Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis |
| title_full_unstemmed | Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis |
| title_short | Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis |
| title_sort | lactate activates er stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis |
| topic | Pulmonary fibrosis Lactate Endoplasmic reticulum stress Caspase-12 Alveolar epithelial cells Apoptosis |
| url | https://doi.org/10.1186/s12931-024-03016-5 |
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