ArticleInflammatory bowel diseases2012
AMP-18 facilitates assembly and stabilization of tight junctions to protect the colonic mucosal barrier.
Article in Inflammatory bowel diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Role of Rho GTPases in inflammatory bowel disease.Cell death discovery · 2023Review
- Beneficial effects of nutritional supplements on intestinal epithelial barrier functions in experimental colitis modelsWorld journal of gastroenterology · 2019Review
- Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn's disease.Therapeutic advances in gastroenterology · 2019Article
- Brain-derived neurotrophic factor preserves intestinal mucosal barrier function and alters gut microbiota in mice.The Kaohsiung journal of medical sciences · 2018Article
- Molecular pathways driving disease-specific alterations of intestinal epithelial cells.Cellular and molecular life sciences : CMLS · 2017Review
- Interplay of GTPases and Cytoskeleton in Cellular Barrier Defects during Gut Inflammation.Frontiers in immunology · 2017Review
- Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota.Nutrition reviews · 2016Review
- A Novel Peptide for Simultaneously Enhanced Treatment of Head and Neck Cancer and Mitigation of Oral Mucositis.PloS one · 2016Article
- Antrum Mucosal Protein-18 Peptide Targets Tight Junctions to Protect and Heal Barrier Structure and Function in Models of Inflammatory Bowel Disease.Inflammatory bowel diseases · 2015Article
- Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2.Histochemistry and cell biology · 2015Article
- AMP-18 Targets p21 to Maintain Epithelial Homeostasis.PloS one · 2015Article
- Small GTPases of the Ras superfamily regulate intestinal epithelial homeostasis and barrier function via common and unique mechanisms.Tissue barriers · 2013Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInflammatory bowel disease (IBD) is characterized by an injured epithelium. Development of agents that could enhance mucosal healing is a major goal in IBD therapeutics. The 18-kDa antrum mucosal protein (AMP-18) and a 21-mer peptide derived from AMP-18 stimulate accumulation of tight junction (TJ) proteins in cultured epithelial cells and mouse colonic mucosa to protect the mucosal barrier, suggesting it might be a useful agent to treat IBD.
methodsWe searched for molecular mechanisms by which AMP peptide or recombinant AMP-18 act on TJs in intact cell monolayers, or those disrupted by low-calcium medium. Roles of the p38 mitogen-activated protein kinase (MAPK) / heat shock protein (hsp)25 pathway and PKCζ were investigated by immunoblotting and confocal microscopy.
resultsAMP peptide activated p38 MAPK, which subsequently phosphorylated hsp25. Accumulated phospho-hsp25 was associated with perijunctional actin. AMP-18 also induced rapid phosphorylation of PKCζ and its colocalization with perijunctional actin in Caco2/bbe cells, which was accompanied by translocation and formation of complexes of "polarity proteins" in the TJ-containing detergent-insoluble fraction. Treatment with AMP-18 also stimulated accumulation of ZO-1, ZO-2, and JAM-A in nascent TJs known to associate with the multimeric p-PKCζ/Par6/ Cdc42/ECT2·GTP/Par3 polarity protein complex.
conclusionsAMP-18 facilitates translocation and assembly of multiple proteins into TJs and their association with and subsequent stabilization of the actin filament network. We speculate that improved barrier function induced by AMP-18 is mediated by enhanced TJ assembly. Thus, AMP-18 may provide a promising lead to develop agents effective in healing injured colonic epithelium in IBD.
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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.