Hyaluronan 35 kDa enhances epithelial barrier function and protects against the development of murine necrotizing enterocolitis
| Autor: | Zhongxin Yu, Aarthi Gunasekaran, Carol A. de la Motte, Sean P. Kessler, Wei Zheng, Hala Chaaban, Kathryn Burge, Jeffrey Eckert |
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| Rok vydání: | 2019 |
| Předmět: |
Occludin
Article Proinflammatory cytokine Tight Junctions Glycosaminoglycan 03 medical and health sciences Mice 0302 clinical medicine Enterocolitis Necrotizing 030225 pediatrics medicine Animals Hyaluronic Acid Intestinal Mucosa Barrier function Enterocolitis Intestinal permeability Tight junction Chemistry medicine.disease Molecular biology digestive system diseases Disease Models Animal Klebsiella pneumoniae Pediatrics Perinatology and Child Health Necrotizing enterocolitis medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Pediatric research |
| ISSN: | 1530-0447 |
| Popis: | Background Disruption of tight junctions (TJs) predisposes to bacterial translocation, intestinal inflammation, and necrotizing enterocolitis (NEC). Previously, studies showed that hyaluronan (HA), a glycosaminoglycan in human milk, maintains intestinal permeability, enhances intestinal immunity, and reduces intestinal infections. In this study, we investigated the effects of HA 35 kDa on a NEC-like murine model. Methods Pups were divided into Sham, NEC, NEC+HA 35, and HA 35. Severity of intestinal injury was compared using a modified macroscopic gut scoring and histologic injury grading. The effect of HA 35 on intestinal permeability was determined by measuring FITC dextran and bacterial translocation. RNA and protein expression of TJ proteins (claudin-2, -3, -4, occludin, and ZO-1) were compared between the groups. Results Pups in the NEC+HA 35 group had increased survival and lower intestinal injury compared to untreated NEC. In addition, HA 35 reduced intestinal permeability, bacterial translocation, and proinflammatory cytokine release. Ileal expression of claudin-2, -3, -4, occludin, and ZO-1 was upregulated in NEC+HA 35 and HA 35 compared to untreated NEC and shams. Conclusion These findings suggest that HA 35 protects against NEC partly by upregulating intestinal TJs and enhancing intestinal barrier function. |
| Databáze: | OpenAIRE |
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