Evidence map›Paper›PMID 32433978›Full record

ArticleGastroenterology2020

Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function.

Caroline H T Hall, J Scott Lee, Emily M Murphy, Mark E Gerich, Rachael Dran, Louis E Glover, Zuhair I Abdulla, Matthew R Skelton, Sean P Colgan

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2023
    Pooled it
  2. Article
  3. Review
  4. Creatine kinase regulates energy metabolism and growth of trophoblasts.bioRxiv : the preprint server for biology · 2026
    Article
  5. Metabolite mimicry identifies butyrate analogs with select protective functions in the intestinal mucosa.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

9 authors at 5 institutions in 3 countries.

Caroline H T HallDivision of Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado, Aurora, Colorado; Mucosal Inflammation Program, University of Colorado, Aurora, Colorado.
J Scott LeeMucosal Inflammation Program, University of Colorado, Aurora, Colorado; Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado.
Emily M MurphyDivision of Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado, Aurora, Colorado; Mucosal Inflammation Program, University of Colorado, Aurora, Colorado; Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado.
Mark E GerichMucosal Inflammation Program, University of Colorado, Aurora, Colorado; Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado.
Rachael DranMucosal Inflammation Program, University of Colorado, Aurora, Colorado; Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado.
Louis E GloverMucosal Inflammation Program, University of Colorado, Aurora, Colorado; Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado; School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
Zuhair I AbdullaDepartment of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, Ohio.
Matthew R SkeltonDepartment of Pediatrics, University of Cincinnati, Cincinnati, Ohio; Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, Ohio.
Sean P ColganMucosal Inflammation Program, University of Colorado, Aurora, Colorado; Division of Gastroenterology and Hepatology, University of Colorado, Aurora, Colorado. Electronic address: sean.colgan@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USChildren's Hospital Colorado · USCincinnati Children's Hospital Medical Center · USTrinity College Dublin · IEUniversity of Colorado Hospital · US

Funding

NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Edward L Melanson · 1995 to 2026
$32.6M
Institutional Training Grant in Pediatric GastroenterologyT32DK067009 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI RONALD J. SOKOL, Edwin Fulco de Zoeten · 2005 to 2026
$7.1M
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
Institutional Career Development CoreKL2TR002534 · NCATS · UNIVERSITY OF COLORADO DENVER · PI BURNHAM, ELLEN L · 2018 to 2022
$4.6M
Hypoxia, HIF, and Mucosal InflammationR37DK050189 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI COLGAN, SEAN P · 2010 to 2019
$4.1M
GASTROINTESTINAL DISEASE TRAINING GRANTT32DK007038 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI COLGAN, SEAN P · 1986 to 2020
$3.5M
METABOLIC CONTROL OF EPITHELIAL AUTOPHAGY DURING INFLAMMATIONR01DK103712 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI COLGAN, SEAN P · 2015 to 2019
$1.7M
PMN-EPITHELIAL CROSSTALK COORDINATES MONOCYTE POLARIZATION DURING INFLAMMATIONR01DK103639 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI CAMPBELL, ERIC LEO · 2014 to 2016
$890k
The role of Na+, K+-ATPase function in Creatine Transporter DeficiencyR21HD080910 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI SKELTON, MATTHEW R · 2015 to 2016
$441k
BLRD VA I01 BX002182NCATS NIH HHS KL2 TR002534NCATS NIH HHS UL1 TR002535NICHD NIH HHS R21 HD080910NIDDK NIH HHS F32 DK122741NIDDK NIH HHS P30 DK048520NIDDK NIH HHS R01 DK050189NIDDK NIH HHS R01 DK095491NIDDK NIH HHS R01 DK103639NIDDK NIH HHS R01 DK103712NIDDK NIH HHS R01 DK104713NIDDK NIH HHS R29 DK050189NIDDK NIH HHS R37 DK050189NIDDK NIH HHS T32 DK007038NIDDK NIH HHS T32 DK067009NINDS NIH HHS R21 NS111217
6 · The paper itself

Abstract

BACKGROUND &

aimsPatients with inflammatory bowel diseases (IBDs) have intestinal barrier dysfunction. Creatine regulates energy distribution within cells and reduces the severity of colitis in mice. We studied the functions of the creatine transporter solute carrier family 6 member 8 (SLC6A8, also called CRT) in intestinal epithelial cells (IECs) and mice, and we measured levels in mucosal biopsies from patients with IBD.

methodsColon biopsy specimens from patients with IBD (30 with Crohn's disease and 27 with ulcerative colitis) and 30 patients without IBD (control individuals) and colon tissues from mice (with and without disruption of Crt) were analyzed by immunofluorescence, immunoblots, and/or quantitative reverse-transcription polymerase chain reaction (qRT-PCR). CRT was knocked down or overexpressed in T84 cells, which were analyzed by immunofluorescence, immunoblots, high-performance liquid chromatography (to measure creatine levels), qRT-PCR, transepithelial electrical resistance, barrier function, actin localization, wound healing, mitochondrial oxygen consumption, and glycolysis extracellular acidification rate assays. Organoids from colon cells of CRT-knockout mice and control mice were analyzed by qRT-PCR, immunoblot, and transepithelial electrical resistance.

resultsCRT localized around tight junctions (TJs) of T84 IECs. In analyses of IECs with CRT knockdown or overexpression, we found that CRT regulates intracellular creatine, barrier formation, and wound healing. CRT-knockout organoids also had diminished barrier formation. In the absence of adequate creatine, IECs transition toward a stressed, glycolysis-predominant form of metabolism; this resulted in leaky TJs and mislocalization of actin and TJ proteins. Colon tissues from patients with IBD had reduced levels of CRT messenger RNA compared with those from control individuals.

conclusionsIn an analysis of IEC cell lines and colonoids derived from CRT-knockout mice, we found that CRT regulates energy balance in IECs and thereby epithelial integrity and barrier function. Mucosal biopsy specimens from patients with ulcerative colitis and inactive Crohn's disease have lower levels of CRT, which might contribute to the reduced barrier function observed in patients with IBD.

Indexed as

AdultAnimalsBiopsyCase-Control StudiesCell LineColitis, UlcerativeColonCrohn DiseaseEnergy MetabolismEpithelial CellsFemaleGene Knockdown TechniquesHumansIntestinal MucosaMaleMembrane Transport Proteinscreatine transporterMembrane Transport ProteinsNerve Tissue ProteinsPlasma Membrane Neurotransmitter Transport ProteinsSLC6A8 protein, humanActinCDClaudinUC

Identifiers

PMID32433978
PMCPMC7891846
OpenAlexW3025043511

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Registered trials

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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.