Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells
Abstract Sepsis-induced lung injury is a serious complication that contributes to the high morbidity and mortality rates in septic patients. This study aims to identify genes associated with sepsis-induced lung injury and evaluate the role of cathepsin B (CTSB) in this process. Here, by analyzing th...
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BMC
2025-05-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02679-0 |
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| author | Xiaobo Zhang Zhuojun Deng Xinyu Zhang Qian Xu Li Liu Dong Yang Zimeng Guo |
| author_facet | Xiaobo Zhang Zhuojun Deng Xinyu Zhang Qian Xu Li Liu Dong Yang Zimeng Guo |
| author_sort | Xiaobo Zhang |
| collection | DOAJ |
| description | Abstract Sepsis-induced lung injury is a serious complication that contributes to the high morbidity and mortality rates in septic patients. This study aims to identify genes associated with sepsis-induced lung injury and evaluate the role of cathepsin B (CTSB) in this process. Here, by analyzing three data sets of sepsis-induced lung injury in mouse models, we identified 23 common differentially expressed genes and performed enrichment analyses. Further experiments demonstrated that CTSB expression was significantly upregulated in the sepsis mouse model, and pre-treatment with the CTSB inhibitor CA-074 markedly improved the survival rate of the mice from 21.05 to 78.95%. In addition, the CTSB inhibitor reduced the systemic inflammatory response in septic mice by decreasing plasma levels of nitric oxide (NO) and the inflammatory cytokines TNF-α and IL-1β.Histological analysis showed that the CTSB inhibitor effectively suppressed CLP-induced lung tissue alterations and neutrophil infiltration, and significantly reduced the expression of inducible nitric oxide synthase (iNOS). Analysis of cell death indicated that the CTSB inhibitor decreased cell death in the lung tissue of CLP mice, particularly by inhibiting the upregulation of gasdermin D-N (GSDMD-N), which is associated with pyroptosis. Furthermore, in vitro experiments revealed that overexpression of CTSB enhanced cell death and promoted pyroptosis in lung epithelial cells. These results indicate that CTSB plays a crucial role in sepsis-induced lung injury, potentially exacerbating the inflammatory response by promoting pyroptosis. Therefore, CTSB may be a potential therapeutic target for sepsis-induced lung injury. |
| format | Article |
| id | doaj-art-a9db3a5d5e784874beb603e36cc66963 |
| institution | OA Journals |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | European Journal of Medical Research |
| spelling | doaj-art-a9db3a5d5e784874beb603e36cc669632025-08-20T01:52:29ZengBMCEuropean Journal of Medical Research2047-783X2025-05-0130111210.1186/s40001-025-02679-0Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cellsXiaobo Zhang0Zhuojun Deng1Xinyu Zhang2Qian Xu3Li Liu4Dong Yang5Zimeng Guo6Department of Emergency, Hebei Medical University Third HospitalDepartment of Emergency, Hebei Medical University Third HospitalDepartment of Emergency, Hebei Medical University Third HospitalDepartment of Emergency, Hebei Medical University Third HospitalDepartment of Emergency, Hebei Medical University Third HospitalDepartment of Emergency, Hebei Medical University Third HospitalDepartment of Rehabilitation, Hebei Medical University Third Hospital Abstract Sepsis-induced lung injury is a serious complication that contributes to the high morbidity and mortality rates in septic patients. This study aims to identify genes associated with sepsis-induced lung injury and evaluate the role of cathepsin B (CTSB) in this process. Here, by analyzing three data sets of sepsis-induced lung injury in mouse models, we identified 23 common differentially expressed genes and performed enrichment analyses. Further experiments demonstrated that CTSB expression was significantly upregulated in the sepsis mouse model, and pre-treatment with the CTSB inhibitor CA-074 markedly improved the survival rate of the mice from 21.05 to 78.95%. In addition, the CTSB inhibitor reduced the systemic inflammatory response in septic mice by decreasing plasma levels of nitric oxide (NO) and the inflammatory cytokines TNF-α and IL-1β.Histological analysis showed that the CTSB inhibitor effectively suppressed CLP-induced lung tissue alterations and neutrophil infiltration, and significantly reduced the expression of inducible nitric oxide synthase (iNOS). Analysis of cell death indicated that the CTSB inhibitor decreased cell death in the lung tissue of CLP mice, particularly by inhibiting the upregulation of gasdermin D-N (GSDMD-N), which is associated with pyroptosis. Furthermore, in vitro experiments revealed that overexpression of CTSB enhanced cell death and promoted pyroptosis in lung epithelial cells. These results indicate that CTSB plays a crucial role in sepsis-induced lung injury, potentially exacerbating the inflammatory response by promoting pyroptosis. Therefore, CTSB may be a potential therapeutic target for sepsis-induced lung injury.https://doi.org/10.1186/s40001-025-02679-0SepsisCathepsin BInflammationPyroptosisGasdermin D |
| spellingShingle | Xiaobo Zhang Zhuojun Deng Xinyu Zhang Qian Xu Li Liu Dong Yang Zimeng Guo Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells European Journal of Medical Research Sepsis Cathepsin B Inflammation Pyroptosis Gasdermin D |
| title | Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells |
| title_full | Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells |
| title_fullStr | Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells |
| title_full_unstemmed | Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells |
| title_short | Inhibiting cathepsin B alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells |
| title_sort | inhibiting cathepsin b alleviates acute lung injury caused by sepsis through suppression of pyroptosis in lung epithelial cells |
| topic | Sepsis Cathepsin B Inflammation Pyroptosis Gasdermin D |
| url | https://doi.org/10.1186/s40001-025-02679-0 |
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