Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13
Abstract Background Sepsis is a systemic inflammatory response caused by infection. When this inflammatory response spreads to the lungs, it can lead to acute lung injury (ALI) or more severe acute respiratory distress syndrome (ARDS). Pulmonary fibrosis is a potential complication of these conditio...
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BMC
2025-01-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-024-03045-0 |
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| author | Cheng Tan Hang Zhou Qiangfei Xiong Xian Xian Qiyuan Liu Zexin Zhang Jingjing Xu Hao Yao |
| author_facet | Cheng Tan Hang Zhou Qiangfei Xiong Xian Xian Qiyuan Liu Zexin Zhang Jingjing Xu Hao Yao |
| author_sort | Cheng Tan |
| collection | DOAJ |
| description | Abstract Background Sepsis is a systemic inflammatory response caused by infection. When this inflammatory response spreads to the lungs, it can lead to acute lung injury (ALI) or more severe acute respiratory distress syndrome (ARDS). Pulmonary fibrosis is a potential complication of these conditions, and the early occurrence of pulmonary fibrosis is associated with a higher mortality rate. The underlying mechanism of ARDS-related pulmonary fibrosis remains unclear. Methods To evaluate the role of mast cell in sepsis-induced pulmonary fibrosis and elucidate its molecular mechanism. We investigated the level of mast cell and epithelial-mesenchymal transition(EMT) in LPS-induced mouse model and cellular model. We also explored the influence of cromolyn sodium and mast cell knockout on pulmonary fibrosis. Additionally, we explored the effect of MC-derived IL-13 on the EMT and illustrated the relationship between mast cell and pulmonary fibrosis. Results Mast cell was up-regulated in the lung tissues of the pulmonary fibrotic mouse model compared to control groups. Cromolyn sodium and mast cell knockout decreased the expression of EMT-related protein and IL-13, alleviated the symptoms of pulmonary fibrosis in vivo and in vitro. The PI3K/AKT/mTOR signaling was activated in fibrotic lung tissue, whereas Cromolyn sodium and mast cell knockout inhibited this pathway. Conclusion The expression level of mast cell is increased in fibrotic lungs. Cromolyn sodium intervention and mast cell knockout alleviate the symptoms of pulmonary fibrosis probably via the PI3K/AKT/mTOR signaling pathway. Therefore, mast cell inhibition is a potential therapeutic target for sepsis-induced pulmonary fibrosis. |
| format | Article |
| id | doaj-art-15eeab6636d343f9837134430a5f9859 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-15eeab6636d343f9837134430a5f98592025-01-12T12:36:41ZengBMCRespiratory Research1465-993X2025-01-0126111810.1186/s12931-024-03045-0Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13Cheng Tan0Hang Zhou1Qiangfei Xiong2Xian Xian3Qiyuan Liu4Zexin Zhang5Jingjing Xu6Hao Yao7Department of Anesthesiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical CenterDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Anesthesiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical CenterDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityAbstract Background Sepsis is a systemic inflammatory response caused by infection. When this inflammatory response spreads to the lungs, it can lead to acute lung injury (ALI) or more severe acute respiratory distress syndrome (ARDS). Pulmonary fibrosis is a potential complication of these conditions, and the early occurrence of pulmonary fibrosis is associated with a higher mortality rate. The underlying mechanism of ARDS-related pulmonary fibrosis remains unclear. Methods To evaluate the role of mast cell in sepsis-induced pulmonary fibrosis and elucidate its molecular mechanism. We investigated the level of mast cell and epithelial-mesenchymal transition(EMT) in LPS-induced mouse model and cellular model. We also explored the influence of cromolyn sodium and mast cell knockout on pulmonary fibrosis. Additionally, we explored the effect of MC-derived IL-13 on the EMT and illustrated the relationship between mast cell and pulmonary fibrosis. Results Mast cell was up-regulated in the lung tissues of the pulmonary fibrotic mouse model compared to control groups. Cromolyn sodium and mast cell knockout decreased the expression of EMT-related protein and IL-13, alleviated the symptoms of pulmonary fibrosis in vivo and in vitro. The PI3K/AKT/mTOR signaling was activated in fibrotic lung tissue, whereas Cromolyn sodium and mast cell knockout inhibited this pathway. Conclusion The expression level of mast cell is increased in fibrotic lungs. Cromolyn sodium intervention and mast cell knockout alleviate the symptoms of pulmonary fibrosis probably via the PI3K/AKT/mTOR signaling pathway. Therefore, mast cell inhibition is a potential therapeutic target for sepsis-induced pulmonary fibrosis.https://doi.org/10.1186/s12931-024-03045-0LPSPulmonary fibrosisMast cellIL-13Cromolyn sodiumSepsis |
| spellingShingle | Cheng Tan Hang Zhou Qiangfei Xiong Xian Xian Qiyuan Liu Zexin Zhang Jingjing Xu Hao Yao Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13 Respiratory Research LPS Pulmonary fibrosis Mast cell IL-13 Cromolyn sodium Sepsis |
| title | Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13 |
| title_full | Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13 |
| title_fullStr | Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13 |
| title_full_unstemmed | Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13 |
| title_short | Cromolyn sodium reduces LPS-induced pulmonary fibrosis by inhibiting the EMT process enhanced by MC-derived IL-13 |
| title_sort | cromolyn sodium reduces lps induced pulmonary fibrosis by inhibiting the emt process enhanced by mc derived il 13 |
| topic | LPS Pulmonary fibrosis Mast cell IL-13 Cromolyn sodium Sepsis |
| url | https://doi.org/10.1186/s12931-024-03045-0 |
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