Affiliation:
1. Department of Neonatology Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital) Wuxi China
2. State Key Laboratory of Reproductive Medicine, Research Institute for Reproductive Health and Genetic Diseases, Wuxi Maternity and Child Health Care Hospital Women's Hospital of Jiangnan University, Jiangnan University Wuxi China
3. Department of Neonatology The Affiliated Wuxi Children's Hospital of Nanjing Medical University Wuxi Jiangsu China
4. Department of Gastroenterology and Digestive Diseases The First Affiliated Hospital of Soochow University Suzhou Jiangsu China
Abstract
AbstractIntestinal dysbiosis is believed to play a role in the development of necrotizing enterocolitis (NEC). The efficacy of JNK‐inhibitory peptide (CPJIP) in treating NEC was assessed. Treatment with CPJIP led to a notable reduction in p‐JNK expression in IEC‐6 cells and NEC mice. Following LPS stimulation, the expression of RNA and protein of claudin‐1, claudin‐3, claudin‐4 and occludin was significantly decreased, with this decrease being reversed by CPJIP administration, except for claudin‐3, which remained consistent in NEC mice. Moreover, the expression levels of the inflammatory factors TNF‐α, IL‐1β and IL‐6 were markedly elevated, a phenomenon that was effectively mitigated by the addition of CPJIP in both IEC‐6 cells and NEC mice. CPJIP administration resulted in improved survival rates, ameliorated microscopic intestinal mucosal injury, and increased the total length of the intestines and colon in NEC mice. Additionally, CPJIP treatment led to a reduction in serum concentrations of FD‐4, D‐lactate and DAO. Furthermore, our results revealed that CPJIP effectively inhibited intestinal cell apoptosis and promoted cell proliferation in the intestine. This study represents the first documentation of CPJIP's ability to enhance the expression of tight junction components, suppress inflammatory responses, and rescue intestinal cell fate by inhibiting JNK activation, ultimately mitigating intestinal severity. These findings suggest that CPJIP has the potential to serve as a promising candidate for the treatment of NEC.
Funder
National Natural Science Foundation of China
Cited by
1 articles.
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