GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway
The activation of inflammatory macrophages plays a pivotal role in the development of liver fibrosis (LF). Ferroptosis contributes to the clearance of inflammatory macrophages and the release of profibrotic factors. Glycyrrhetic Acid 3-O-Mono-β-d-glucuronide (GAMG) is a natural compound, the potenti...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725000229 |
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| author | Qing Pang Shuai Zhou Yong Wang Hongtao Pan Zhicheng Wang Xiliang Qin Chao Zhu Shilei Chen Huichun Liu Xiaosi Hu Hao Jin |
| author_facet | Qing Pang Shuai Zhou Yong Wang Hongtao Pan Zhicheng Wang Xiliang Qin Chao Zhu Shilei Chen Huichun Liu Xiaosi Hu Hao Jin |
| author_sort | Qing Pang |
| collection | DOAJ |
| description | The activation of inflammatory macrophages plays a pivotal role in the development of liver fibrosis (LF). Ferroptosis contributes to the clearance of inflammatory macrophages and the release of profibrotic factors. Glycyrrhetic Acid 3-O-Mono-β-d-glucuronide (GAMG) is a natural compound, the potential role of which on LF remains uncertain. In this study, GAMG treatment significantly reduced hepatocyte steatosis, fibroplasia, inflammatory cell infiltration, and collagen fiber deposition in LF mice. In addition, GAMG remarkably decreased the content of collagen protein and improved liver function indicators. Single-cell RNA sequencing revealed that GAMG significantly affected the changes of macrophage subsets in LF, and Funrich analysis identified IRF1 as a key transcription factor regulating the macrophage genome. IRF1 was significantly increased while ferroptosis related SLC7A11 was significantly down-regulated in GAMG treated inflammatory macrophages. Mass spectrometry metabolomics analysis showed that GAMG significantly affected metabolites associated with LF. In vivo and in vitro experiments further verified that GAMG induced ferroptosis of inflammatory macrophages through the IRF1/SLC7A11 axis, and ultimately alleviated LF. Therefore, GAMG induces ferroptosis of inflammatory macrophages by activating the IRF1/SLC7A11 axis, which provides a new strategy for the treatment of LF. |
| format | Article |
| id | doaj-art-5232dc4b5a99495bb68721ff0d7ccccc |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-5232dc4b5a99495bb68721ff0d7ccccc2025-08-20T02:15:24ZengElsevierRedox Biology2213-23172025-03-018010350910.1016/j.redox.2025.103509GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathwayQing Pang0Shuai Zhou1Yong Wang2Hongtao Pan3Zhicheng Wang4Xiliang Qin5Chao Zhu6Shilei Chen7Huichun Liu8Xiaosi Hu9Hao Jin10Department of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, ChinaDepartment of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Corresponding author.Department of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Corresponding author. Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China.Department of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China; Corresponding author. Department of Hepatopancreatobiliary Surgery, Anhui No.2 Provincial People’s Hospital, Hefei, 230041, China.The activation of inflammatory macrophages plays a pivotal role in the development of liver fibrosis (LF). Ferroptosis contributes to the clearance of inflammatory macrophages and the release of profibrotic factors. Glycyrrhetic Acid 3-O-Mono-β-d-glucuronide (GAMG) is a natural compound, the potential role of which on LF remains uncertain. In this study, GAMG treatment significantly reduced hepatocyte steatosis, fibroplasia, inflammatory cell infiltration, and collagen fiber deposition in LF mice. In addition, GAMG remarkably decreased the content of collagen protein and improved liver function indicators. Single-cell RNA sequencing revealed that GAMG significantly affected the changes of macrophage subsets in LF, and Funrich analysis identified IRF1 as a key transcription factor regulating the macrophage genome. IRF1 was significantly increased while ferroptosis related SLC7A11 was significantly down-regulated in GAMG treated inflammatory macrophages. Mass spectrometry metabolomics analysis showed that GAMG significantly affected metabolites associated with LF. In vivo and in vitro experiments further verified that GAMG induced ferroptosis of inflammatory macrophages through the IRF1/SLC7A11 axis, and ultimately alleviated LF. Therefore, GAMG induces ferroptosis of inflammatory macrophages by activating the IRF1/SLC7A11 axis, which provides a new strategy for the treatment of LF.http://www.sciencedirect.com/science/article/pii/S2213231725000229Glycyrrhetic acid 3-O-Mono-β-d-glucuronideLiver fibrosisFerroptosisInflammatory macrophagesIRF1SLC7A11 |
| spellingShingle | Qing Pang Shuai Zhou Yong Wang Hongtao Pan Zhicheng Wang Xiliang Qin Chao Zhu Shilei Chen Huichun Liu Xiaosi Hu Hao Jin GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway Redox Biology Glycyrrhetic acid 3-O-Mono-β-d-glucuronide Liver fibrosis Ferroptosis Inflammatory macrophages IRF1 SLC7A11 |
| title | GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway |
| title_full | GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway |
| title_fullStr | GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway |
| title_full_unstemmed | GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway |
| title_short | GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway |
| title_sort | gamg alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the irf1 slc7a11 signaling pathway |
| topic | Glycyrrhetic acid 3-O-Mono-β-d-glucuronide Liver fibrosis Ferroptosis Inflammatory macrophages IRF1 SLC7A11 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725000229 |
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