| Autor: |
Le, Huijuan, Wang, Yanyan, Zhou, Jiefei, Li, Dan, Gong, Zizhen, Zhu, Fangxinxing, Wang, Jian, Tian, Chunyan, Cai, Wei, Wu, Jin |
| Zdroj: |
Mucosal immunology; October 2024, Vol. 17 Issue: 5 p1060-1071, 12p |
| Abstrakt: |
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants and the most common cause of neonatal death, whereas the molecular mechanism of intestinal injury remains unclear accompanied by deficiency of effective therapeutic approaches. GIT2 (G-protein-coupled receptor kinase interacting proteins 2) can affect innate and adaptive immunity and has been involved in multiple inflammatory disorders. In this study, we investigated whether GIT2 participates in the pathogenesis of NEC. Here we found that intestinal Git2gene expression was significantly increased in NEC patients and NEC mice, which positively correlated with the tissue damage severity, and Git2deficiency could potently protect against NEC development in mice. Mechanistically, Git2gene knockout dramatically increased the recruitment of MDSCs in the intestine, and in vivodepletion of MDSCs almost completely abrogated the protective effect of Git2deficiency on NEC. Moreover, Git2deficiency induced MDSCs intestinal accumulation mainly relied on CXCL1/CXCL12 signaling, as evidenced by the significant increment of CXCL1 and CXCL12 levels in intestinal epithelium of Git2-/-mice and dramatically decrease of MDSCs accumulation in intestine as well as increase of NEC severity upon treatment of CXCL1/CXCL12 pathway inhibitors. In addition, Git2deficiency induced up-regulation of CXCL1 and CXCL12 is at least partially mediated through activating NF-κB signaling. Thus, our findings suggest that GIT2 is involved in the pathogenesis of NEC, and targeting GIT2 may be a potential preventive and therapeutic approach for NEC. |
| Databáze: |
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