Evidence map›Paper›PMID 25701737›Full record

ArticleGastroenterology2015

Chromosome-associated protein D3 promotes bacterial clearance in human intestinal epithelial cells by repressing expression of amino acid transporters.

Andrew T Schuster, Craig R Homer, Jacqueline R Kemp, Kourtney P Nickerson, Emily Deutschman, Yeojung Kim, Gail West, Tammy Sadler, Eleni Stylianou, Dawid Krokowski and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. FBXO6 mediated ubiquitination of SLC3A2 drives ferroptosis in ulcerative colitis: a machine learning and SHAP discovery.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
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  14. Condensin action and compaction.Current genetics · 2019
    Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Acupuncture and regulation of gastrointestinal function.World journal of gastroenterology · 2015
    Review
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

16 authors at 2 institutions in 1 country.

Andrew T Schuster *Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Craig R Homer *Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Jacqueline R KempDepartment of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Kourtney P NickersonDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Emily DeutschmanDepartment of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Yeojung KimDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Gail WestDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Tammy SadlerDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Eleni StylianouDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Dawid KrokowskiDepartment of Pharmacology, Case Western Reserve University, Cleveland, Ohio.
Maria HatzoglouDepartment of Pharmacology, Case Western Reserve University, Cleveland, Ohio.
Carol de la MotteDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Brian P RubinDepartment of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Claudio FiocchiDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Christine McDonaldDepartment of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Michelle S LongworthDepartment of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Cleveland Clinic Lerner College of Medicine · USCase Western Reserve University · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
VERSICAN PROTEOLYSIS AND REGULATION OF VASCULAR SMOOTH MUSCLEP01HL107147 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI LAUER, MARK E · 2011 to 2017
$16.1M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Theresa Torres Pizarro · 2015 to 2026
$15.6M
Regulation of Gene Expression During StressR01DK053307 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI HATZOGLOU, MARIA · 1998 to 2021
$9.6M
Translational Control by Osmotically Active SolutesR37DK060596 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI HATZOGLOU, MARIA · 2011 to 2020
$5.3M
Cell interactions in the inflammed intestinal mucosaR01DK050984 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI FIOCCHI, CLAUDIO · 1995 to 2014
$3.1M
Autophagy and Nod2 Function in Crohn's DiseaseR01DK082437 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI MCDONALD, CHRISTINE L · 2009 to 2013
$1.6M
Condensin-mediated genome organization and transcriptional regulationR01GM102400 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI LONGWORTH, MICHELLE S · 2012 to 2016
$1.5M
Epithelial Cell-Derived IL-1-alpha as a Novel Danger Signal in IBD PathogenesisR01DK093630 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI FIOCCHI, CLAUDIO · 2012 to 2015
$1.4M
NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1TR000439NHLBI NIH HHS P01 HL107147NIDDK NIH HHS P30 DK097948NIDDK NIH HHS R01 DK050984NIDDK NIH HHS R01DK050984NIDDK NIH HHS R01 DK053307NIDDK NIH HHS R01DK053307NIDDK NIH HHS R01 DK082437NIDDK NIH HHS R01DK082437NIDDK NIH HHS R01 DK093630NIDDK NIH HHS R37 DK060596NIDDK NIH HHS R37DK060596NIGMS NIH HHS R01 GM102400NIGMS NIH HHS R01GM102400
6 · The paper itself

Abstract

BACKGROUND &

aimsDefects in colonic epithelial barrier defenses are associated with ulcerative colitis (UC). The proteins that regulate bacterial clearance in the colonic epithelium have not been completely identified. The Drosophila chromosome-associated protein D3 (dCAP-D3) regulates responses to bacterial infection. We examined whether CAP-D3 promotes bacterial clearance in human colonic epithelium.

methodsClearance of Salmonella or adherent-invasive Escherichia coli LF82 was assessed by gentamycin protection assays in HT-29 and Caco-2 cells expressing small hairpin RNAs against CAP-D3. We used immunoblot assays to measure levels of CAP-D3 in colonic epithelial cells from patients with UC and healthy individuals (controls). RNA sequencing identified genes activated by CAP-D3. We analyzed the roles of CAP-D3 target genes in bacterial clearance using gentamycin protection and immunofluorescence assays and studies with pharmacologic inhibitors.

resultsCAP-D3 expression was reduced in colonic epithelial cells from patients with active UC. Reduced CAP-D3 expression decreased autophagy and impaired intracellular bacterial clearance by HT-29 and Caco-2 colonic epithelial cells. Lower levels of CAP-D3 increased transcription of genes encoding SLC7A5 and SLC3A2, the products of which heterodimerize to form an amino acid transporter in HT-29 cells after bacterial infection; levels of SLC7A5-SLC3A2 were increased in tissues from patients with UC compared with controls. Reduced CAP-D3 in HT-29 cells resulted in earlier recruitment of SLC7A5 to Salmonella-containing vacuoles, increased activity of mTORC1, and increased survival of bacteria. Inhibition of SLC7A5-SLC3A2 or mTORC1 activity rescued the bacterial clearance defects of CAP-D3-deficient cells.

conclusionsCAP-D3 down-regulates transcription of genes that encode amino acid transporters (SLC7A5 and SLC3A2) to promote bacterial autophagy by colon epithelial cells. Levels of CAP-D3 protein are reduced in patients with active UC; strategies to increase its levels might restore mucosal homeostasis to patients with active UC.

Indexed as

Adenosine TriphosphatasesAutophagyCaco-2 CellsCell Cycle ProteinsColitis, UlcerativeCrohn DiseaseDrosophila ProteinsEpithelial CellsEscherichia coliFusion Regulatory Protein 1, Heavy ChainGene Expression RegulationHT29 CellsHumansImmunity, InnateIntestinal MucosaLarge Neutral Amino Acid-Transporter 1Adenosine TriphosphatasesCAP-D3 protein, DrosophilaCell Cycle ProteinsDrosophila ProteinsFusion Regulatory Protein 1, Heavy ChainLarge Neutral Amino Acid-Transporter 1Mechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNCAPD3 protein, humanSLC3A2 protein, humanTOR Serine-Threonine KinasesCondensinDysbiosisInflammatory Bowel DiseaseInnate Immunity

Identifiers

PMID25701737
PMCPMC4446190
OpenAlexW2108068656

What OpenQuestion holds

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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.