Bibliographic Details
| Title: |
Disruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis |
| Authors: |
Dongdong Wang, Yanxia Li, Hao Yang, Xiaoqi Shen, Xiaolin Shi, Chenyu Li, Yongjing Zhang, Xiaoyu Liu, Bin Jiang, Xudong Zhu, Hanwen Zhang, Xiaoyu Li, Hui Bai, Qing Yang, Wei Gao, Fang Bai, Yong Ji, Qi Chen, Jingjing Ben |
| Source: |
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| More Details: |
Abstract Macrophage-orchestrated inflammation contributes to multiple diseases including sepsis. However, the underlying mechanisms remain to be defined clearly. Here, we show that macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is up-regulated in murine sepsis models. When myeloid Tigar is ablated, sepsis induced by either lipopolysaccharide treatment or cecal ligation puncture in male mice is attenuated via inflammation inhibition. Mechanistic characterizations indicate that TIGAR directly binds to transforming growth factor β-activated kinase (TAK1) and promotes tumor necrosis factor receptor-associated factor 6-mediated ubiquitination and auto-phosphorylation of TAK1, in which residues 152-161 of TIGAR constitute crucial motif independent of its phosphatase activity. Interference with the binding of TIGAR to TAK1 by 5Z-7-oxozeaenol exhibits therapeutic effects in male murine model of sepsis. These findings demonstrate a non-canonical function of macrophage TIGAR in promoting inflammation, and confer a potential therapeutic target for sepsis by disruption of TIGAR-TAK1 interaction. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-48708-0 |
| Access URL: |
https://doaj.org/article/c7ad10500ead469595b8dfe398035605 |
| Accession Number: |
edsdoj.7ad10500ead469595b8dfe398035605 |
| Database: |
Directory of Open Access Journals |
