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Updated: Nov 20, 2025
08:42
A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis
Published on: April 10, 2019
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DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing
Li Lu1, Weijue Xu1, Jiangbin Liu1
1Department of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Digestive Diseases and Sciences
|January 20, 2021
Summary
Developmentally regulated GTP-binding protein 1 (DRG1) is crucial for intestinal barrier integrity. Its deficiency increases permeability, highlighting RAC1 inhibitors as a potential treatment for necrotizing enterocolitis (NEC) in newborns.
Area of Science:
- Neonatal Medicine
- Gastroenterology
- Molecular Biology
Background:
- Immature intestine is a primary risk factor for necrotizing enterocolitis (NEC), a severe neonatal intestinal disease.
- Developmentally regulated GTP-binding protein 1 (DRG1) plays a role in intestinal maturation.
Purpose of the Study:
- To elucidate the function of DRG1 in the pathogenesis of NEC.
- To investigate the molecular mechanisms by which DRG1 influences intestinal barrier function.
Main Methods:
- DRG1 expression analysis via immunohistochemistry and qPCR.
- Identification of DRG1 interacting proteins using immunoprecipitation and mass spectrometry.
- In vitro studies using Caco2 and FHs74Int cells with DRG1 manipulation to assess cell junctions and barrier permeability.
Main Results:
- DRG1 expression decreased in NEC ileum, correlating with compromised cell junctions.
- DRG1 deficiency destabilized E-cadherin and occludin, increasing epithelial permeability.
- DRG1 overexpression protected against LPS-induced barrier disruption and maintained cell integrity.
- DRG1 regulates RAC1 activity to maintain adherens junctions and intestinal barrier integrity.
Conclusions:
- DRG1 deficiency impairs epithelial barrier function by disrupting cell junctions.
- RAC1 inhibition demonstrates therapeutic potential for protecting against NEC-induced intestinal injury.
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