Evidence map›Paper›PMID 33471252›Full record

ArticleDigestive diseases and sciences2021

DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing Enterocolitis.

Li Lu, Weijue Xu, Jiangbin Liu, Liping Chen, Shaohua Hu, Qingfeng Sheng, Minghua Zhang, Zhibao Lv

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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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5citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Necrotizing Enterocolitis: Overview on In Vitro Models.International journal of molecular sciences · 2021
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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Li LuDepartment of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Weijue XuDepartment of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Jiangbin LiuDepartment of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Liping ChenDepartment of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Shaohua HuDepartment of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Qingfeng ShengDepartment of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China.
Minghua ZhangClinical Pharmacy Laboratory, Chinese PLA General Hospital, Beijing, 100853, China.
Zhibao LvDepartment of General Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200040, China. zhibaolyu@163.com.ORCID 0000-0002-6854-1394

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AminoquinolinesAnimalsAntigens, CDCaco-2 CellsCadherinsElectric ImpedanceEnterocolitis, NecrotizingEnzyme InhibitorsEpithelial CellsGTP-Binding ProteinsHEK293 CellsHumansIntercellular JunctionsIntestinal MucosaMiceOccludinAminoquinolinesAntigens, CDCadherinsCDH1 protein, humandevelopmentally regulated GTP-binding proteinEnzyme InhibitorsGTP-Binding ProteinsNSC 23766OccludinOCLN protein, humanPyrimidinesrac1 GTP-Binding ProteinRAC1 protein, humanCell–cell junctionDRG1E-cadherinIntestinal barrier permeabilityNecrotizing enterocolitisRAC1

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.