ArticleGastroenterology2023
Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification.
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Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Spermidine in Colorectal cancer: friend or foe?Amino acids · 2026Review
- Polydopamine cross-linked Bifidobacterium single cell core-shell system with multi-target regulation to alleviate constipation in mice.Archives of microbiology · 2026Article
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation.Amino acids · 2026Article
- Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.Nature cell biology · 2025Article
- Protective role of epithelial deoxyhypusine synthase in colorectal carcinogenesis caused by deletion of the adenomatous polyposis coli gene.Cancer letters · 2025Article
- Polyamine metabolism in cancer: drivers of immune evasion, ferroptosis and therapy resistance.Expert reviews in molecular medicine · 2025Review
- Epithelial Hypusination Regulates Helicobacter pylori-induced Gastric Inflammation.Research square · 2025Article
- eIF5A maintains intestinal epithelial homeostasis by sustaining intestinal stem cells.Cell regeneration (London, England) · 2025Article
- Spermine oxidase promotes Helicobacter pylori-mediated gastric carcinogenesis through acrolein production.Oncogene · 2025Article
- Aconitate Decarboxylase 1 Downregulates Colitis and Maintains Homeostasis of the Gut Metabolome and Microbiome.Gastro hep advances · 2025Article
- Platelet activation in patients with peripheral artery disease from 43 sites: Assessment of samples transported by overnight mail.JVS-vascular insights · 2025Article
- Engineered spermidine-secretingFrontiers in neuroscience · 2025Article
- The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice.Amino acids · 2024Article
- Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.Nature communications · 2024Article
- The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.International journal of molecular sciences · 2024Review
- Analysis of the effect of hypusination in myeloid cells on colitis and colitis-associated cancer.Heliyon · 2024Article
- Review
- Aryl hydrocarbon receptor confers protection against macrophage pyroptosis and intestinal inflammation through regulating polyamine biosynthesis.Theranostics · 2024Article
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Authors and funding
21 authors at 4 institutions in 1 country.
Alain P GobertDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: alain.p.gobert@vumc.org.
Thaddeus M SmithDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Yvonne L LatourDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
Mohammad AsimDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Daniel P BarryDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Margaret M AllamanDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Kamery J WilliamsDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Kara M McNamaraDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
Alberto G DelgadoDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Sarah P ShortDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee.
Raghavendra G MirmiraKovler Diabetes Center, Department of Medicine, The University of Chicago, Chicago, Illinois.
Kristie L RoseDepartment of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Kevin L ScheyDepartment of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Irene Zagol-IkapitteWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Jeremy S ColemanWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Olivier BoutaudWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Shilin ZhaoDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
M Blanca PiazueloDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee.
M Kay WashingtonCenter for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
Lori A CoburnDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.
Keith T WilsonDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee. Electronic address: keith.wilson@vumc.org.
Vanderbilt University Medical Center · USVanderbilt University · USVA Tennessee Valley Healthcare System · USUniversity of Chicago · US
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MRole of Iron and B-Catenin Activation in Gastric CarcinogenesisP01CA116087 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 2009 to 2026
$27.5MPilot and Feasibility ProgramP30DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2013 to 2026
$20.9MProject 3 - Molecular Signatures of Gastric Carcinogenesis in the Host Response to H. pyloriP01CA028842 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1985 to 2019
$15.8MTennessee Valley Cooperative Human Tissue NetworkUM1CA183727 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2014 to 2026
$12.6MMULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4MTranscriptional Mechanisms Governing Beta Cell DifferentiationR01DK060581 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Raghavendra G Mirmira · 2002 to 2026
$8.5MRole of Polyamines and Hypusine in Nutrient-Induced Beta-Cell Growth and ReplicationR01DK124906 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2020 to 2026
$4.0MSpermidine as a New Therapy for Colitis and Chemopreventive for Colitis-associated CarcinogenesisR01DK128200 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 2021 to 2024
$2.7MImmunological Mechanisms of Disease Training ProgramT32AI138932 · NIAID · VANDERBILT UNIVERSITY · PI MAJOR, AMY S, RATHMELL, JEFFREY C. · 2019 to 2023
$1.4MAntioxidant regulation of intestinal homeostasis and diseaseK01DK123495 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHORT, SARAH PALMER · 2020 to 2024
$732kBLRD VA I01 BX004366CSRD VA I01 CX002171CSRD VA I01 CX002473NCI NIH HHS P01 CA028842NCI NIH HHS P01 CA116087NCI NIH HHS P30 CA068485NCI NIH HHS R41 CA257262NCI NIH HHS T32 CA009592NCI NIH HHS UM1 CA183727NIAID NIH HHS T32 AI138932NIDDK NIH HHS K01 DK123495NIDDK NIH HHS P30 DK020595NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK060581NIDDK NIH HHS R01 DK124906NIDDK NIH HHS R01 DK128200
Abstract
BACKGROUND &
aimsThe amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5A
methodsWe used human colon tissue messenger RNA samples and publicly available transcriptomic datasets, tissue microarrays, and patient-derived colon organoids. Mice with intestinal epithelial-specific deletion of Dhps were investigated at baseline and in models of colitis and colon carcinogenesis.
resultsWe found that patients with ulcerative colitis and Crohn's disease exhibit reduced colon levels of DHPS messenger RNA and DHPS protein and reduced levels of EIF5A
conclusionsHypusination in intestinal epithelial cells has a key role in the prevention of colitis and colorectal cancer, and enhancement of this pathway via supplementation of spermidine could have a therapeutic impact.
Indexed as
ColitisSpermidineAnimalsCarcinogenesisHomeostasisHumansInflammationMicePeptide Initiation FactorsProteomicsPeptide Initiation FactorsSpermidineColon CancerHypusineInflammationIntestinal Epithelial Cells
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