ArticleCell proliferation2019
Inhibition of CREB-mediated ZO-1 and activation of NF-κB-induced IL-6 by colonic epithelial MCT4 destroys intestinal barrier function.
Article in Cell proliferation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 96 citations in OpenAlex.
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- Genome-Guided Probiotic Mechanisms of Enterococcus hirae SMU2502: Wnt/β-catenin-Driven Intestinal Epithelial Proliferation and Protection Against Salmonella Infection.Probiotics and antimicrobial proteins · 2026Article
- Thymic Stromal Lymphopoietin-Driven B-Cell Hyperactivation Impairs Intestinal Epithelial Homeostasis Predisposing to Enterocolitis in Hirschsprung Disease.Cellular and molecular gastroenterology and hepatology · 2026Article
- Anti-inflammatory effect of pirfenidone compared to dexamethasone in ulcerative colitis model induced by acetic acid in rats: involvement of miR-146a and TLR4/NF-κB signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Role of lactylation-induced macrophage failed phenotypic switching in sustaining inflammation of diabetic wounds.Frontiers in immunology · 2026Review
- Regulation of Intestinal Butyrate Transporters by Oxidative and Inflammatory Status.Antioxidants (Basel, Switzerland) · 2025Review
- SLC16A3 as an immunosuppressive Kupffer cell marker predicts poor prognosis in HBV-positive hepatocellular carcinoma.Journal of translational medicine · 2025Article
- Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review).International journal of molecular medicine · 2025Review
- Improved prebiotic-based "shield" equipped probiotics for enhanced colon cancer therapy by polarizing M1 macrophages and regulating intestinal microbiota.Acta pharmaceutica Sinica. B · 2025Article
- Ubiquitination-mediated upregulation of glycolytic enzyme MCT4 in promoting astrocyte reactivity during neuroinflammation.Journal of neuroinflammation · 2025Article
- SLC7A11 in Fibrosis: Molecular Mechanisms and Future Prospects.Aging and disease · 2025Review
- Lactate and lactylation: emerging roles in autoimmune diseases and metabolic reprogramming.Frontiers in immunology · 2025Review
- MCT4 inhibition attenuates inflammatory response toFrontiers in immunology · 2025Article
- GZMA suppressed GPX4-mediated ferroptosis to improve intestinal mucosal barrier function in inflammatory bowel disease.Cell communication and signaling : CCS · 2024Article
- Beneficial effect of heat-killed Lactiplantibacillus plantarum L-137 on intestinal barrier function of rat small intestinal epithelial cells.Scientific reports · 2024Article
- Emerging roles of lactate in acute and chronic inflammation.Cell communication and signaling : CCS · 2024Review
- Resveratrol Alleviates Zearalenone-Induced Intestinal Dysfunction in Mice through the NF-κB/Nrf2/HO-1 Signalling Pathway.Foods (Basel, Switzerland) · 2024Article
- β-carotene inhibits MAPKs signaling pathways on rat colonic epithelial cells to attenuate TNF-α-induced intestinal inflammation and injury.Cell biochemistry and biophysics · 2024Article
- Rabeprazole suppressed gastric intestinal metaplasia through activation of GPX4-mediated ferroptosis.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveInflammatory bowel disease (IBD) is a disorder intestinal inflammation and impaired barrier function, associated with increased epithelial expression of monocarboxylate transporter 4 (MCT4). However, the specific non-metabolic function and clinical relevance of MCT4 in IBD remain to be fully elucidated.
methodsLentivirus-mediated overexpression of MCT4 was used to assess the role of MCT4 in transcriptionally regulating ZO-1 and IL-6 expression by luciferase assays, WB and ChIP. IP was used to analyse the effect of MCT4 on the interaction NF-κB-CBP or CREB-CBP, and these MCT4-mediated effects were confirmed in vivo assay.
resultsWe showed that ectopic expression of MCT4 inhibited ZO-1 expression, while increased pro-inflammatory factors expression, leading to destroy intestinal epithelial barrier function in vitro and in vivo. Mechanistically, MCT4 contributed NF-κB p65 nuclear translocation and increased the binding of NF-κB p65 to the promoter of IL-6, which is attributed to MCT4 enhanced NF-κB-CBP interaction and dissolved CREB-CBP complex, resulting in reduction of CREB activity and CREB-mediated ZO-1 expression. In addition, treatment of experimental colitis with MCT4 inhibitor α-cyano-4-hydroxycinnamate (CHC) ameliorated mucosal intestinal barrier function, which was due to attenuation of pro-inflammation factors expression and enhancement of ZO-1 expression.
conclusionThese findings suggested a novel role of MCT4 in controlling development of IBD and provided evidence for potential targets of IBD.
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