ArticleDigestive diseases and sciences2021
DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing Enterocolitis.
Article in Digestive diseases and sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Global transcriptional analysis of human FHs 74 Int intestinal epithelial cells after exposure to advanced glycation end products.PloS one · 2025Article
- Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage.Stem cell research & therapy · 2024Article
- The biochemical effects of carotenoids in orange carrots on the colonic proteome in a mouse model of diet-induced obesity.Frontiers in nutrition · 2024Article
- Transepithelial Barrier Dysfunction Drives Microbiota Dysbiosis to Initiate Epithelial Clock-driven Inflammation.Journal of Crohn's & colitis · 2023Article
- Necrotizing Enterocolitis: Overview on In Vitro Models.International journal of molecular sciences · 2021Review
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8 authors.
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Abstract
backgroundAn immature intestine is a high-risk factor for necrotizing enterocolitis (NEC), which is a serious intestinal disease in newborns. The regulation of developmentally regulated GTP-binding protein 1 (DRG1) during organ development suggests a potential role of DRG1 in the maturation process of the intestine.
aimTo illustrate the function of DRG1 during the pathogenesis of NEC.
methodsDRG1 expression in the intestine was measured using immunohistochemistry and q-PCR. Immunoprecipitation coupled with mass spectrometry was used to identify the interacting proteins of DRG1. The biological functions of the potential interactors were annotated with the Database for Annotation, Visualization and Integrated Discovery. Caco2 and FHs74Int cells with stable DRG1 silencing or overexpression were used to investigate the influence of DRG1 on cell junctions and intestinal barrier permeability and to elucidate the downstream mechanism.
resultsDRG1 was constitutively expressed during the intestinal maturation process but significantly decreased in the ileum in the context of NEC. Protein interaction analysis revealed that DRG1 was closely correlated with cell junctions. DRG1 deficiency destabilized the E-cadherin and occludin proteins near the cell membrane and increased the permeability of the epithelial cell monolayer, while DRG1 overexpression prevented lipopolysaccharide-induced disruption of E-cadherin and occludin expression and cell monolayer integrity. Further investigation suggested that DRG1 maintained cell junctions, especially adherens junctions, by regulating RAC1 activity, and RAC1 inhibition with NSC23766 attenuated intestinal injury and led to improved barrier integrity in experimental NEC.
conclusionsOur findings illustrate the mechanism underlying the effect of DRG1 deficiency on epithelial cell permeability regulation and provide evidence supporting the application of RAC1 inhibitors for protection against NEC.
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