ArticleMolecular biology of the cell2000
Restoration of tight junction structure and barrier function by down-regulation of the mitogen-activated protein kinase pathway in ras-transformed Madin-Darby canine kidney cells.
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 271 citations in OpenAlex.
- Plant-derived betaine enhances barrier integrity and immune responses in canine intestinal epithelial cells and macrophages under endotoxin challenge.Journal of animal science · 2026Article
- Co-trimoxazole-induced reproductive toxicity and placental-barrier disruption: impact on cell-cell junctions and ERK signaling pathway.Frontiers in cell and developmental biology · 2026Article
- Architecture, permeability, disruption dynamics and remodeling of tight junction proteins: Implications for performance, health, and welfare of the broiler chicken.Poultry science · 2026Review
- Proton pump inhibitor increases intestinal epithelial paracellular permeability via the p38-MAPK/NF-κB signaling pathway.Molecular biology reports · 2025Article
- Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer.Current issues in molecular biology · 2023Article
- Trans-Compartmental Regulation of Tight Junction Barrier Function.Tissue barriers · 2023Review
- Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super-resolution microscopy.Annals of the New York Academy of Sciences · 2022Article
- Association Between Proton Pump Inhibitor Therapy and Spontaneous Bacterial Peritonitis Occurrence in Cirrhotic Patients: A Clinical Review.Current medical science · 2022Review
- Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age.Nature communications · 2022Article
- Half-Sandwich Arene Ruthenium(II) Thiosemicarbazone Complexes: Evaluation of Anticancer Effect on Primary and Metastatic Ovarian Cancer Cell Lines.Frontiers in pharmacology · 2022Article
- Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction.Molecular therapy. Nucleic acids · 2021Article
- Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival.Molecular biomedicine · 2021Article
- Ethanol-induced lymphatic endothelial cell permeability via MAP-kinase regulation.American journal of physiology. Cell physiology · 2021Article
- Article
- Innate immune mechanisms to oral pathogens in oral mucosa of HIV-infected individuals.Oral diseases · 2020Review
- Treatment of diabetic retinopathy through neuropeptide Y-mediated enhancement of neurovascular microenvironment.Journal of cellular and molecular medicine · 2020Article
- Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization.Scientific reports · 2019Article
- Review
- Article
- ZO-1 protein is required for hydrogen peroxide to increase MDCK cell paracellular permeability in an ERK 1/2-dependent manner.American journal of physiology. Cell physiology · 2018Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In the Madin-Darby canine kidney epithelial cell line, the proteins occludin and ZO-1 are structural components of the tight junctions that seal the paracellular spaces between the cells and contribute to the epithelial barrier function. In Ras-transformed Madin-Darby canine kidney cells, occludin, claudin-1, and ZO-1 were absent from cell-cell contacts but were present in the cytoplasm, and the adherens junction protein E-cadherin was weakly expressed. After treatment of the Ras-transformed cells with the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059, which blocks the activation of mitogen-activated protein kinase (MAPK), occludin, claudin-1, and ZO-1 were recruited to the cell membrane, tight junctions were assembled, and E-cadherin protein expression was induced. Although it is generally believed that E-cadherin-mediated cell-cell adhesion is required for tight junction assembly, the recruitment of occludin to the cell-cell contact area and the restoration of epithelial cell morphology preceded the appearance of E-cadherin at cell-cell contacts. Both electron microscopy and a fourfold increase in the transepithelial electrical resistance indicated the formation of functional tight junctions after MEK1 inhibition. Moreover, inhibition of MAPK activity stabilized occludin and ZO-1 by differentially increasing their half-lives. We also found that during the process of tight junction assembly after MEK1 inhibition, tyrosine phosphorylation of occludin and ZO-1, but not claudin-1, increased significantly. Our study demonstrates that down-regulation of the MAPK signaling pathway causes the restoration of epithelial cell morphology and the assembly of tight junctions in Ras-transformed epithelial cells and that tyrosine phosphorylation of occludin and ZO-1 may play a role in some aspects of tight junction formation.
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Registered trials
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.