Evidence map›Paper›PMID 29487135›Full record

ArticleThe Journal of biological chemistry2018

Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function.

J Scott Lee, Ruth X Wang, Erica E Alexeev, Jordi M Lanis, Kayla D Battista, Louise E Glover, Sean P Colgan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 149 citations in OpenAlex.

  1. Trial
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  13. Gut microbes · 2025
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  14. A scalable long-termbioRxiv : the preprint server for biology · 2025
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  15. DNA-utilization loci enable exogenous DNA metabolism in gut Bacteroidales.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Review
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33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

J Scott LeeFrom the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and.
Ruth X WangFrom the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and.
Erica E AlexeevFrom the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and.
Jordi M LanisFrom the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and.
Kayla D BattistaFrom the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and.
Louise E Gloverthe School of Medicine, University College Dublin, Dublin, Ireland.
Sean P ColganFrom the Department of Medicine and the Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado 80045 and sean.colgan@ucdenver.edu.
University of Colorado Denver · USUniversity College Dublin · IE

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Paul S. Maclean · 1995 to 2026
$32.6M
ROLE OF EPITHELIA IN ISCHEMIA/REPERFUSION INJURYR01DK050189 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI COLGAN, SEAN P · 2000 to 2024
$5.0M
Mechanisms of Adenosine ProtectionR01DK095491 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Sean P Colgan · 2012 to 2026
$4.9M
Metabolic Regulation of Inflammation by Microbial SCFAR01DK104713 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Sean P Colgan · 2015 to 2026
$4.7M
Hypoxia, HIF, and Mucosal InflammationR37DK050189 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI COLGAN, SEAN P · 2010 to 2019
$4.1M
Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)T32GM136444 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MICHAEL A MCMURRAY, Rytis Prekeris · 2020 to 2026
$3.7M
METABOLIC CONTROL OF EPITHELIAL AUTOPHAGY DURING INFLAMMATIONR01DK103712 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI COLGAN, SEAN P · 2015 to 2019
$1.7M
Microbial-derived factors regulating mucosal wound healingF30DK120072 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI WANG, RUTH XINHE · 2019 to 2022
$145k
Microbial-derived purines in intestinal homeostasisF32DK122741 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LEE, JOSEPH SCOTT · 2019 to 2021
$140k
Metabolic Regulation of Mucosal InflammationI01BX002182 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI COLGAN, SEAN P · 2014 to 2025
–
EPITHELIA AND ISCHEMIA/REPERFUSION INJURYR29DK050189 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI COLGAN, SEAN P · 1995 to 1999
–
BLRD VA I01 BX002182NIDDK NIH HHS F30 DK120072NIDDK NIH HHS F32 DK122741NIDDK NIH HHS P30 DK048520NIDDK NIH HHS R01 DK050189NIDDK NIH HHS R01 DK095491NIDDK NIH HHS R01 DK103712NIDDK NIH HHS R01 DK104713NIDDK NIH HHS R29 DK050189NIDDK NIH HHS R37 DK050189NIGMS NIH HHS T32 GM136444
6 · The paper itself

Abstract

Intestinal epithelial cells form a selectively permeable barrier to protect colon tissues from luminal microbiota and antigens and to mediate nutrient, fluid, and waste flux in the intestinal tract. Dysregulation of the epithelial cell barrier coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically depleting state of physiological hypoxia. However, studies that systematically examine energy flux and adenylate metabolism during intestinal epithelial barrier development and restoration after disruption are lacking. Here, to delineate barrier-related energy flux, we developed an HPLC-based profiling method to track changes in energy flux and adenylate metabolites during barrier development and restoration. Cultured epithelia exhibited pooling of phosphocreatine and maintained ATP during barrier development. EDTA-induced epithelial barrier disruption revealed that hypoxanthine levels correlated with barrier resistance. Further studies uncovered that hypoxanthine supplementation improves barrier function and wound healing and that hypoxanthine appears to do so by increasing intracellular ATP, which improved cytoskeletal G- to F-actin polymerization. Hypoxanthine supplementation increased the adenylate energy charge in the murine colon, indicating potential to regulate adenylate energy charge-mediated metabolism in intestinal epithelial cells. Moreover, experiments in a murine colitis model disclosed that hypoxanthine loss during active inflammation correlates with markers of disease severity. In summary, our results indicate that hypoxanthine modulates energy metabolism in intestinal epithelial cells and is critical for intestinal barrier function.

Indexed as

Energy MetabolismAnimalsColitisColonFemaleHypoxanthineIntestinal MucosaMetabolomeMiceMice, Inbred C57BLOxygen ConsumptionPermeabilityTight JunctionsHypoxanthinebarrier functioncolitiscytoskeletonenergy metabolismepitheliaintestinal epitheliumintestinal metabolismtight junction

Identifiers

PMID29487135
PMCPMC5912467
OpenAlexW2791881958

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.