ArticleInternational journal of molecular medicine2017
AGR2 ameliorates tumor necrosis factor-α-induced epithelial barrier dysfunction via suppression of NF-κB p65-mediated MLCK/p-MLC pathway activation.
Article in International journal of molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
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- Regulatory effects of the p38 mitogen-activated protein kinase-myosin light chain kinase pathway on the intestinal epithelial mechanical barrier and the mechanism of modified Pulsatilla decoction in the treatment of ulcerative colitis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
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- The role of mir-197-3p in regulating the tight junction permeability of celiac disease patients under gluten free diet.Molecular biology reports · 2023Article
- MicroRNA-29b-3p promotes intestinal permeability in IBS-D via targeting TRAF3 to regulate the NF-κB-MLCK signaling pathway.PloS one · 2023Article
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- Shenling Baizhu Powder Alleviates TNBS-Induced Colitis in Rats by Improving Intestinal Epithelial Permeability and Inhibiting Inflammation Through the TLR5/MyD88/NF-κB Pathway.Frontiers in pharmacology · 2022Article
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- Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn's Disease Fibrosis.Journal of Crohn's & colitis · 2021Article
- Effect of short-time treatment with TNF-α on stem cell activity and barrier function in enteroids.Cytotechnology · 2021Article
- Corticosteroid enhances epithelial barrier function in intestinal organoids derived from patients with Crohn's disease.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Phosphorylated‑myosin light chain mediates the destruction of small intestinal epithelial tight junctions in mice with acute liver failure.Molecular medicine reports · 2021Article
- Anagliptin Protected against Hypoxia/Reperfusion-Induced Brain Vascular Endothelial Permeability by Increasing ZO-1.ACS omega · 2021Article
- Anterior Gradient Protein 2 Promotes Mucosal Repair in Pediatric Ulcerative Colitis.BioMed research international · 2021Article
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2 authors at 1 institution in 1 country.
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Abstract
Intestinal epithelial barrier dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Anterior gradient protein 2 homologue (AGR2) assists in maintaining intestinal homeostasis in dextran sulphate sodium-induced mouse ileocolitis; however, it is unclear whether it modulates intestinal barrier function. Our study aimed to investigate the protective role of AGR2 in tumor necrosis factor (TNF)-α-induced intestinal epithelial barrier injury. Caco-2 cell monolayers were pre-transfected with an AGR2 plasmid and then exposed to TNF-α. Epithelial permeability was assessed by detecting transepithelial electrical resistance and fluorescein isothiocyanate-dextran (40 kDa) flux. The protein expression levels of zonula occludens-1 (ZO-1), occludin, claudin-1, myosin light chain kinase (MLCK)/p-MLC, and nuclear factor (NF)-κB p65 were determined by western blotting. In addition, the cellular distributions of ZO-1, occludin, F-actin, and NF-κB p65 were evaluated by immunofluorescence staining. The results showed that the AGR2 mRNA and protein expression levels were both decreased in the Caco-2 cell monolayers, while AGR2 overexpression significantly ameliorated TNF-α-induced epithelial barrier hyperpermeability, increased the expression of tight junction (TJ) proteins and stabilized the cytoskeletal structure. Furthermore, AGR2 inhibited the changes in MLCK, MLC and p-MLC expression in response to TNF-α stimulation. Collectively, our study suggests that AGR2 inhibits TNF-α‑induced Caco-2 cell hyperpermeability by regulating TJ and that this protective mechanism may be promoted by inhibition of NF-κB p65-mediated activation of the MLCK/p-MLC signaling pathway.
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