Protein 4.1R regulates M1 macrophages polarization via glycolysis, alleviating sepsis-induced liver injury in mice
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved..
Acute liver injury (ALI) is a common clinical disease caused by sepsis, metabolic syndrome, hepatitis virus. Macrophage plays an important role in the development of ALI, which is characterized by polarization and inflammatory regulation. The polarization process of macrophages is related to membrane binding proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in cell activation and cytokine secretion. However, whether protein 4.1R is involved in regulating macrophage polarization and inflammation-induced liver injury remains unknown. In this study, protein 4.1R is identified with the special effect on macrophage M1 polarization. And it is further demonstrated that protein 4.1R deficiency significantly enhance glycolytic metabolism. Mechanistically, the regulation of protein 4.1R on pyruvate kinase M2 (PKM2) plays a key role in glycolysis metabolism. In addition, we found that protein 4.1R directly interacts with toll-like receptor 4 (TLR4), inhibits the activation of the AKT/HIF-1α signaling pathway. In conclusion, protein 4.1R targets HIF-1α mediated glycolysis regulates M1 macrophage polarization, indicating that protein 4.1R is a candidate for regulating macrophage mediated inflammatory response. In conclusion, we have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy. We have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:128 |
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| Enthalten in: |
International immunopharmacology - 128(2024) vom: 15. Feb., Seite 111546 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sang, Si-Yao [VerfasserIn] |
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| Links: |
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| Themen: |
AKT/HIF-1α signal pathway |
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| Anmerkungen: |
Date Completed 08.02.2024 Date Revised 08.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111546 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367277263 |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Acute liver injury (ALI) is a common clinical disease caused by sepsis, metabolic syndrome, hepatitis virus. Macrophage plays an important role in the development of ALI, which is characterized by polarization and inflammatory regulation. The polarization process of macrophages is related to membrane binding proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in cell activation and cytokine secretion. However, whether protein 4.1R is involved in regulating macrophage polarization and inflammation-induced liver injury remains unknown. In this study, protein 4.1R is identified with the special effect on macrophage M1 polarization. And it is further demonstrated that protein 4.1R deficiency significantly enhance glycolytic metabolism. Mechanistically, the regulation of protein 4.1R on pyruvate kinase M2 (PKM2) plays a key role in glycolysis metabolism. In addition, we found that protein 4.1R directly interacts with toll-like receptor 4 (TLR4), inhibits the activation of the AKT/HIF-1α signaling pathway. In conclusion, protein 4.1R targets HIF-1α mediated glycolysis regulates M1 macrophage polarization, indicating that protein 4.1R is a candidate for regulating macrophage mediated inflammatory response. In conclusion, we have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy. We have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AKT/HIF-1α signal pathway | |
| 650 | 4 | |a Acute liver injury | |
| 650 | 4 | |a Glycolysis | |
| 650 | 4 | |a M1 macrophage polarization | |
| 650 | 4 | |a Protein 4.1R | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 700 | 1 | |a Wang, Yuan-Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Taotao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jiao-Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Qiao-Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ting |e verfasserin |4 aut | |
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