ArticleGastroenterology2013
TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
207 citing papers in PubMed, 393 citations in OpenAlex.
- Effects of bromelain supplementation on disease activity and quality of life in patients with ulcerative colitis: a randomized, triple-blind, placebo-controlled study.Scientific reports · 2025Trial
- Dysregulated bile acid metabolism impairs intestinal barrier integrity via defective GPBAR1 signaling in low-birth-weight suckling piglet.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6.International journal of molecular sciences · 2026Review
- Coffea arabica pulp aqueous extract exhibits the anti-colitogenic effect in mice: preventive efficacy and possible mechanisms of action.Biological research · 2026Article
- Intestinal T cells in aging: implications for gut barrier integrity and inflammaging.GeroScience · 2026Review
- Targeting MLCK1 uncouples immune checkpoint inhibitor-induced colitis from antitumour immunity.Gut · 2026Article
- Betanin ameliorates dextran sulfate sodium-induced colitis in mice by modulating tight junction protein expression.Biochemistry and biophysics reports · 2026Article
- Ribosome Homeostasis Regulated by SETD2 Preserves Intestinal Epithelial Barrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Preventive Effects of Probiotic and PostbioticJournal of microbiology and biotechnology · 2026Article
- Architecture, permeability, disruption dynamics and remodeling of tight junction proteins: Implications for performance, health, and welfare of the broiler chicken.Poultry science · 2026Review
- Astragaloside IV ameliorates DSS-induced intestinal epithelial barrier dysfunction associated with modulation of tight junction proteins and MLCK/p-MLC and MyD88/TRAF6 signaling pathways.Frontiers in pharmacology · 2026Article
- Dysregulated programmed cell death of intestinal epithelial cells in ulcerative colitis: Molecular mechanisms and novel therapeutic interventions (Review).International journal of molecular medicine · 2025Review
- Dendrobium Officinale-Derived Carbon Dots Nanozymes Alleviate Colitis by Orchestrating Intestinal Mucus-Epithelium-Immune Barriers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the drug repurposing potential of lisinopril against TNBS-induced colitis in Wistar rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.Acta pharmaceutica Sinica. B · 2025Review
- Elevated uric acid induces erectile dysfunction in rats by interacting with MLCK and inhibiting its ubiquitin-mediated degradation.Communications biology · 2025Article
- LAP-Hsp60 complex modulates epithelial tight junction barrier.Research square · 2025Article
- Metrnl protects intestinal barrier function by regulating tight junctions via the IKKβ/IκBα/NFκB/MLCK/MLC signaling pathway.Cell death discovery · 2025Article
- Bisdemethoxycurcumin and Curcumin Alleviate Inflammatory Bowel Disease by Maintaining Intestinal Epithelial Integrity and Regulating Gut Microbiota in Mice.Journal of agricultural and food chemistry · 2025Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsTight junction dysregulation and epithelial damage contribute to barrier loss in patients with inflammatory bowel disease. However, the mechanisms that regulate these processes and their relative contributions to disease pathogenesis are not completely understood. We investigated these processes using colitis models in mice.
methodsWe induced colitis by adoptive transfer of CD4(+)CD45RB(hi) cells or administration of dextran sulfate sodium to mice, including those deficient in tumor necrosis factor receptor (TNFR) 1, TNFR2, or the long isoform of myosin light chain kinase (MLCK). Intestinal tissues and isolated epithelial cells were analyzed by immunoblot, immunofluorescence, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction assays.
resultsInduction of immune-mediated colitis by CD4(+)CD45RB(hi) adoptive transfer increased intestinal permeability, epithelial expression of claudin-2, the long isoform of MLCK, and TNFR2 (but not TNFR1) and phosphorylation of the myosin II light chain. Long MLCK upregulation, myosin II light chain phosphorylation, barrier loss, and weight loss were attenuated in TNFR2(-/-) , but not TNFR1(-/-) , recipients of wild-type CD4(+)CD45RB(hi) cells. Similarly, long MLCK(-/-) mice had limited increases in myosin II light chain phosphorylation, claudin-2 expression, and intestinal permeability and delayed onset of adoptive transfer-induced colitis. However, coincident with onset of epithelial apoptosis, long MLCK(-/-) mice ultimately developed colitis. This indicates that disease progresses via apoptosis in the absence of MLCK-dependent tight junction regulation. In support of this conclusion, long MLCK(-/-) mice were not protected from epithelial apoptosis-mediated, damage-dependent dextran sulfate sodium colitis.
conclusionsIn immune-mediated inflammatory bowel disease models, TNFR2 signaling increases long MLCK expression, resulting in tight junction dysregulation, barrier loss, and induction of colitis. At advanced stages, colitis progresses by apoptosis and mucosal damage that result in tight junction- and MLCK-independent barrier loss. Therefore, barrier loss in immune-mediated colitis occurs via two temporally and morphologically distinct mechanisms. Differential targeting of these mechanisms can lead to improved inflammatory bowel disease therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.