| Autor: |
Yunfei Zhang, Mei Yan, Yingying Xia, Yingbin Yue, Shuli Wang, Yuhui Hu, Genjian Lai, Quanjiang Wu, Qianyang Liu, Xin Ding, Chunbao Guo |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 32, Iss 1, Pp 101214- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2024.101214 |
| Popis: |
Inducible nitric oxide synthase (iNOS), regulated by nuclear factor kappa B (NF-κB), is crucial for intestinal inflammation and barrier injury in the progression of necrotizing enterocolitis (NEC). The NF-κB pathway is inhibited by S-glutathionylation of inhibitory κB kinase β (IKKβ), which can be restored by glutaredoxin-1 (Grx1). Thus, we aim to explore the role of Grx1 in experimental NEC. Wild-type (WT) and Grx1-knockout (Grx1−/−) mice were treated with an NEC-inducing regimen. Primary intestinal epithelial cells (IECs) were subjected to LPS treatment. The production of iNOS, NO, and inflammation injuries were assessed. NF-κB and involved signaling pathways were also explored. The severity of NEC was attenuated in Grx1−/− mice. Grx1 ablation promoted IKKβ glutathionylation, NF-κB inactivation, and decreased iNOS, NO, and O2·– production in NEC mice. Furthermore, Grx1 ablation restrained proinflammatory cytokines and cell apoptosis, ameliorated intestinal barrier damage, and promoted proliferation in NEC mice. Grx1 ablation protected NEC through iNOS and NO inhibition, which related to S-glutathionylation of IKKβ to inhibit NF-κB signaling. Grx1-related signaling pathways provide a new therapeutic target for NEC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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