Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:969 |
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| Enthalten in: |
European journal of pharmacology - 969(2024) vom: 15. März, Seite 176425 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xie, Rong-Cheng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2024.176425 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368777065 |
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| 100 | 1 | |a Xie, Rong-Cheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute kidney injury (AKI) | |
| 650 | 4 | |a C5a receptor | |
| 650 | 4 | |a Gut microbiota | |
| 650 | 4 | |a Gut-kidney axis | |
| 650 | 4 | |a Intestinal mucosal barrier | |
| 650 | 4 | |a W54011 | |
| 650 | 7 | |a N-((4-dimethylaminophenyl)methyl)-N-(4-isopropylphenyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-1-carboxamide |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Receptor, Anaphylatoxin C5a |2 NLM | |
| 650 | 7 | |a Aniline Compounds |2 NLM | |
| 650 | 7 | |a Tetrahydronaphthalenes |2 NLM | |
| 700 | 1 | |a Zhang, Jin-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Xiao-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yu-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lian-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Xiang-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Xue-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Hong-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Li-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jie-Fei |e verfasserin |4 aut | |
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