Evidence map›Paper›PMID 36655602›Full record

ArticleJournal of Crohn's & colitis2023

GATA6-AS1 Regulates Intestinal Epithelial Mitochondrial Functions, and its Reduced Expression is Linked to Intestinal Inflammation and Less Favourable Disease Course in Ulcerative Colitis.

Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina BenShoshan, Kelli L VanDussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of Crohn's & colitis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
6.9field-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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2023
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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

24 authors at 8 institutions in 3 countries.

Katya E SosnovskiSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Tzipi BraunSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Amnon AmirSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Danielle MoshelSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Marina BenShoshanSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Kelli L VanDussenCincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID 0000-0002-5810-0720
Nina LevharSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0001-8834-5991
Haya Abbas-EgbariyaSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Katia BeiderSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Rakefet Ben-YishaySheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Syed Asad AliDepartment of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Sean R MooreDepartment of Pediatrics, University of Virginia, Charlottesville, VA, USA.
Subra KugathasanEmory University, Atlanta, GA, USA.ORCID 0000-0002-8686-4189
Ifat AbramovichThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa, Israel.
Efrat Glick SaarSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Batya WeissSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Iris BarshackSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Eyal GottliebThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Bat Galim, Haifa, Israel.
Tamar GeigerDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shomron Ben-HorinSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.
Igor UlitskyDepartments of Biological Regulation and Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0003-0555-6561
Jeffrey S HyamsConnecticut Children's Medical Center, Hartford, CT, USA.
Lee A DensonCincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID 0000-0001-8045-7198
Yael HabermanSheba Medical Center, Tel-Hashomer, affiliated with the Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0003-2680-1570
Tel Aviv University · ILCincinnati Children's Hospital Medical Center · USTechnion – Israel Institute of Technology · ILWeizmann Institute of Science · ILAga Khan University · PKConnecticut Children's Medical Center · USEmory University · USUniversity of Virginia · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE ARMISTEAD DENSON · 2007 to 2026
$24.4M
Predicting Response to Standardized Pediatric Colitis Therapy: PROTECT StudyU01DK095745 · NIDDK · CONNECTICUT CHILDREN'S MEDICAL CENTER · PI DENSON, LEE ARMISTEAD, HYAMS, JEFFREY SAMUEL · 2012 to 2016
$10.4M
NIDDK NIH HHS 5U01DK095745NIDDK NIH HHS P30 DK078392NIDDK NIH HHS U01 DK095745
6 · The paper itself

Abstract

BACKGROUND AND

aimsWidespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

methodsMucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

resultsGATA6-AS1 showed predominant expression in gut epithelia using single cell datasets. GATA6-AS1 levels were reduced in Crohn's disease [CD] ileum and UC rectum in independent cohorts. Reduced GATA6-AS1 lncRNA was further linked to a more severe UC form, and to a less favourable UC course. The GATA6-AS1 interactome showed robust enrichment for mitochondrial proteins, and included TGM2, an autoantigen in coeliac disease that is induced in UC, CD and coeliac disease, in contrast to GATA6-AS1 reduction in these cohorts. GATA6-AS1 silencing resulted in induction of TGM2, and this was coupled with a reduction in mitochondrial membrane potential and mitochondrial respiration, as well as in a reduction of metabolites linked to aerobic respiration relevant to mucosal inflammation. TGM2 knockdown in GATA6-AS1-deficient cells rescued mitochondrial respiration.

conclusionsGATA6-AS1 levels are reduced in UC, CD and coeliac disease, and in more severe UC forms. We highlight GATA6-AS1 as a target regulating epithelial mitochondrial functions, potentially through controlling TGM2 levels.

Indexed as

Celiac DiseaseColitis, UlcerativeCrohn DiseaseCaco-2 CellsGATA6 Transcription FactorHumansInflammationIntestinal MucosaMitochondriaRectumGATA6 protein, humanGATA6 Transcription FactorGATA6-AS1 long non-coding RNAinflammatory bowel diseasemitochondria

Identifiers

PMID36655602
PMCPMC10274303
OpenAlexW4317479564

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.