Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair
Abstract Background The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflamma...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-022-01030-y |
| _version_ | 1811175761413931008 |
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| author | Xiao-Hu Zhao Ting Yang Meng-Yao Zheng Peinan Zhao Li-Ya An Yu-Xing Qi Ke-Qian Yi Peng-Cheng Zhang Da-Li Sun |
| author_facet | Xiao-Hu Zhao Ting Yang Meng-Yao Zheng Peinan Zhao Li-Ya An Yu-Xing Qi Ke-Qian Yi Peng-Cheng Zhang Da-Li Sun |
| author_sort | Xiao-Hu Zhao |
| collection | DOAJ |
| description | Abstract Background The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. Results We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. Conclusion Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract |
| first_indexed | 2024-04-10T19:42:11Z |
| format | Article |
| id | doaj.art-99455e2eed824af7a30564beea0f05d8 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-10T19:42:11Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-99455e2eed824af7a30564beea0f05d82023-01-29T12:17:47ZengBMCCell Communication and Signaling1478-811X2023-01-0121112010.1186/s12964-022-01030-yCystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repairXiao-Hu Zhao0Ting Yang1Meng-Yao Zheng2Peinan Zhao3Li-Ya An4Yu-Xing Qi5Ke-Qian Yi6Peng-Cheng Zhang7Da-Li Sun8Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Gastroenterology, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Medicine (Alfred Hospital), Central Clinical School, Monash UniversityDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityDepartment of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical UniversityAbstract Background The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. Results We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. Conclusion Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstracthttps://doi.org/10.1186/s12964-022-01030-yEfferocytosisCystathionine gamma-lyase (Cth)Intestinal ischaemiaReperfusion injury (IR)Extracellular signal-regulated kinase 1/2 (ERK12)Intestinal barrier repair |
| spellingShingle | Xiao-Hu Zhao Ting Yang Meng-Yao Zheng Peinan Zhao Li-Ya An Yu-Xing Qi Ke-Qian Yi Peng-Cheng Zhang Da-Li Sun Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair Cell Communication and Signaling Efferocytosis Cystathionine gamma-lyase (Cth) Intestinal ischaemia Reperfusion injury (IR) Extracellular signal-regulated kinase 1/2 (ERK12) Intestinal barrier repair |
| title | Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair |
| title_full | Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair |
| title_fullStr | Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair |
| title_full_unstemmed | Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair |
| title_short | Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair |
| title_sort | cystathionine gamma lyase cth induces efferocytosis in macrophages via erk1 2 to modulate intestinal barrier repair |
| topic | Efferocytosis Cystathionine gamma-lyase (Cth) Intestinal ischaemia Reperfusion injury (IR) Extracellular signal-regulated kinase 1/2 (ERK12) Intestinal barrier repair |
| url | https://doi.org/10.1186/s12964-022-01030-y |
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