ArticleLaboratory investigation; a journal of technical methods and pathology2009
Tumor suppressor FOXO3 participates in the regulation of intestinal inflammation.
Article in Laboratory investigation; a journal of technical methods and pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Population, Epidemiological, and Functional Genetics of Gastric Cancer Candidate Genes in Peruvians with Predominant Amerindian Ancestry.Digestive diseases and sciences · 2016Pooled it
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- "Remodeling the intestinal immune microenvironment": immune regulation and tissue regeneration by mesenchymal stem/stromal cells in the repair microenvironment of inflammatory bowel disease.Frontiers in immunology · 2025Review
- FOXO3: at the crossroads of metabolic, inflammatory, and tumorigenic remodeling in the colon.American journal of physiology. Gastrointestinal and liver physiology · 2024Review
- FOXO3 Deficiency in Neutrophils Drives Colonic Inflammation and Tumorigenesis.International journal of molecular sciences · 2023Article
- Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD.BMJ open gastroenterology · 2023Article
- miRNA Molecules-Late Breaking Treatment for Inflammatory Bowel Diseases?International journal of molecular sciences · 2023Review
- Activation of PI3K/Akt prevents hypoxia/reoxygenation-induced GnRH decline via FOXO3a.Physiological research · 2022Article
- The Association Between Forkhead Box Class O3A Gene Polymorphism and Psoriasis and Its Relationship with Psoriasis Severity.The Journal of clinical and aesthetic dermatology · 2022Article
- FOXO3 Expression in Macrophages Is Lowered by a High-Fat Diet and Regulates Colonic Inflammation and Tumorigenesis.Metabolites · 2022Article
- Effect of circRNA_FOXO3 rs12196996 polymorphism and FOXO3 rs2232365 polymorphism on survival rate and severity of intensive care unit-acquired sepsis.Bioengineered · 2022Article
- Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity.Oncogenesis · 2021Article
- Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion.The Journal of experimental medicine · 2021Article
- MiR-222 inhibition alleviates Staphylococcal Enterotoxin B-induced inflammatory acute lung injury by targeting Foxo3.Journal of biosciences · 2020Article
- FOXO3 is involved in the tumor necrosis factor-driven inflammatory response in fibroblast-like synoviocytes.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Loss of Forkhead Box O3 Facilitates Inflammatory Colon Cancer: Transcriptome Profiling of the Immune Landscape and Novel Targets.Cellular and molecular gastroenterology and hepatology · 2019Article
- Reduced mitochondrial activity in colonocytes facilitates AMPKα2-dependent inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- High-fat diet induced leptin and Wnt expression: RNA-sequencing and pathway analysis of mouse colonic tissue and tumors.Carcinogenesis · 2017Article
- Blunting Autoantigen-induced FOXO3a Protein Phosphorylation and Degradation Is a Novel Pathway of Glucocorticoids for the Treatment of Systemic Lupus Erythematosus.The Journal of biological chemistry · 2016Article
- Intestinal inflammation requires FOXO3 and prostaglandin E2-dependent lipogenesis and elevated lipid droplets.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic mucosal injury and the infiltration of inflammatory cells. Tumor suppressor FOXO3 regulates gene expression and its translocation to the cytosol leads to the abrogation of its transcriptional function. We have previously shown that bacterial infection regulates FOXO3 in intestinal epithelial cells and increases cytokine levels. As TNFalpha is a major contributor in intestinal inflammation, the aim of this study was to assess its effect on FOXO3 and FOXO3's contribution to intestinal inflammation in vitro and in vivo. TNFalpha induces the translocation of nuclear FOXO3 into the cytosol where it undergoes proteasomal degradation in human intestinal HT-29 cells. Proximally, the PI3K and IKK pathways mediate TNFalpha-induced FOXO3 phosphorylation. In FOXO3-silenced HT-29 cells, TNFalpha-induced IL-8 expression is increased approximately 83%. In vivo, Foxo3 is present in the nuclei and cytosol of colonic crypt epithelia. In DSS-induced colonic inflammation, Foxo3's nuclear localization is lost and it is only found in the cytosol. Consistent with a role for Foxo3 in colitis, Foxo3-deficient mice treated with DSS developed more severe colonic inflammation with an increased number of intraepithelial lymphocytes and PMNs infiltrated in the epithelia, than wild-type mice. In summary, TNFalpha inactivates FOXO3 in intestinal epithelia through the PI3K and IKK pathways and FOXO3 inactivation leads to the upregulation of IL-8 in vitro; in vivo Foxo3 is in the cytosol of inflamed colonic epithelia and Foxo3 deficiency leads to severe intestinal inflammation.
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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.