ArticleCell death and differentiation2017
AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 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
132 citing papers in PubMed, 229 citations in OpenAlex.
- The JNK2-microbiome axis modulates gut barrier integrity through microbial acetate.Gut microbes · 2026Article
- The coordinated actions of metformin in the intestine and liver improves hyperglycemia.Cell reports · 2026Article
- Multi-omics Mendelian randomization and experimental validation identify PRKAB1 as a regulator of phosphatidylcholine metabolism in IBD.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Loss of VMP1 Impairs Tight Junction Recycling and Aggravates Intestinal Barrier Dysfunction in Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 4-Methylesculetin improves the growth performance of grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- AMPK Deficiency Induces Corneal Epithelial Barrier Dysfunction by Modulating Energy Homeostasis.Investigative ophthalmology & visual science · 2026Article
- Gut microbiota-derived tryptophan metabolite indole-3-carboxaldehyde enhances intestinal barrier function via aryl hydrocarbon receptor/AMP-activated protein kinase signaling activation.Animal bioscience · 2026Article
- Metabolic reprogramming in ulcerative colitis: integrating dietary drivers, pathogenesis, and therapeutic advances.Frontiers in immunology · 2026Review
- CANDiT: A machine learning framework for differentiation therapy in colorectal cancer.Cell reports. Medicine · 2025Article
- Eicosapentaenoic acid enhances intestinal stem cell-mediated colonic epithelial regeneration by activating the LSD1-WNT signaling pathway.Journal of advanced research · 2025Article
- Macronutrients as Regulators of Intestinal Epithelial Permeability: Where Do We Stand?Comprehensive reviews in food science and food safety · 2025Review
- Plant polysaccharides and antioxidant benefits for exercise performance and gut health: from molecular pathways to clinic.Molecular and cellular biochemistry · 2025Review
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Inulin Diet Alleviates Abdominal Aortic Aneurysm by Increasing Akkermansia and Improving Intestinal Barrier.Biomedicines · 2025Article
- MicroRNAs in Plasma-Derived Extracellular Vesicles as Non-Invasive Biomarkers for Eosinophilic Esophagitis.International journal of molecular sciences · 2025Observational
- Article
- Time-restricted feeding leads to sex- and organ-specific responses in the murine digestive system.PloS one · 2025Article
- Organosilicone double-long-chain diquaternary ammonium salt acts as a biofilm scavenger to ameliorate colitis induced by dextran sulfate sodium salt.Frontiers in immunology · 2025Article
- Article
- Cedrol ameliorates inflammatory bowel disease via mitochondrial biogenesis, gut microbiota restoration, and intestinal barrier repair.Frontiers in pharmacology · 2025Article
72 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Impairment in gut epithelial integrity and barrier function is associated with many diseases. The homeostasis of intestinal barrier is based on a delicate regulation of epithelial proliferation and differentiation. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism, and cellular metabolites are intrinsically involved in epigenetic modifications governing cell differentiation. We aimed to evaluate the regulatory role of AMPK on intestinal epithelial development and barrier function. In this study, AMPK activator (AICAR) improved the barrier function of Caco-2 cells as indicated by increased transepithelial electrical resistance and reduced paracellular FITC-dextran permeability; consistently, AICAR enhanced epithelial differentiation and tight junction formation. Transfection of Caco-2 cells with AMPK WT plasmid, which enhances AMPK activity, improved epithelial barrier function and epithelial differentiation, while K45R (AMPK dominant negative mutant) impaired; these changes were correlated with the expression of caudal type homeobox 2 (CDX2), the key transcription factor committing cells to intestinal epithelial lineage. CDX2 deficiency abolished intestinal differentiation promoted by AMPK activation. Mechanistically, AMPK inactivation was associated with polycomb repressive complex 2 regulated enrichment of H3K27me3, the inhibitory histone modification, and lysine-specific histone demethylase-1-mediated reduction of H3K4me3, a permissive histone modification. Those histone modifications provide a mechanistic link between AMPK and CDX2 expression. Consistently, epithelial AMPK knockout in vivo reduced CDX2 expression, impaired intestinal barrier function, integrity and ultrastructure of tight junction, and epithelial cell migration, promoted intestinal proliferation and exaggerated dextran sulfate sodium-induced colitis. In summary, AMPK enhances intestinal barrier function and epithelial differentiation via promoting CDX2 expression, which is partially mediated by altered histone modifications in the Cdx2 promoter.
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.