Evidence map›Paper›PMID 35021065›Full record

ArticleCell2022

GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis.

Nitish Rana, Giuseppe Privitera, Hannah C Kondolf, Katarzyna Bulek, Susana Lechuga, Carlo De Salvo, Daniele Corridoni, Agne Antanaviciute, Rebecca L Maywald, Alexander M Hurtado and 10 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 142 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed, 2 pooled it
17.9field-weighted citation impact, top 1% 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

142 citing papers in PubMed, 2 syntheses or guidelines pooled it, 206 citations in OpenAlex.

  1. Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026
    Pooled it
  2. Pooled it
  3. Inflammatory bowel disease and breast cancer: epidemiological evidence, shared biology, and clinical management.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  4. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Pyroptosis: Turning Up the Heat on Cancer.Annual review of immunology · 2026
    Review
  17. Article
  18. Review
  19. Single-Cell Genetic Mapping of Gasdermin Expression Across Immune-Mediated Inflammatory Diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  20. Review

82 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 3 countries.

Nitish RanaDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Departments of Physiology & Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Giuseppe PriviteraDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Hannah C KondolfDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Katarzyna BulekDepartment of Inflammation & Immunity, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Susana LechugaDepartment of Inflammation & Immunity, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Carlo De SalvoDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Daniele CorridoniMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Agne AntanaviciuteMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Rebecca L MaywaldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Alexander M HurtadoDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Junjie ZhaoDepartment of Inflammation & Immunity, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Emina H HuangDepartments of Cancer Biology and Colon & Rectal Surgery, Learner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Xiaoxia LiDepartment of Inflammation & Immunity, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
E Ricky ChanInstitute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Alison SimmonsMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Giorgos BamiasAcademic Department of Gastroenterology, Ethnikon & Kapodistriakon University of Athens, Laikon Hospital, Athens, Greece.
Derek W AbbottDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Jason D HeaneyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Andrei I IvanovDepartment of Inflammation & Immunity, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Theresa T PizarroDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address: theresa.pizarro@case.edu.
University School · USCleveland Clinic · USJohn Radcliffe Hospital · GBBaylor College of Medicine · USNational and Kapodistrian University of Athens · GR

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Ubiquitination Pathways Mediating Chronic Intestinal InflammationP01DK091222 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI COMINELLI, FABIO · 2011 to 2020
$16.5M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI AMITABH CHAK · 2015 to 2026
$15.6M
Molecular mechanisms of gasdermin recognition by proteases and autophagy proteins in cytokine releaseP01AI141350 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ABBOTT, DEREK W · 2020 to 2024
$9.4M
CYTOKINES AND INFLAMMATORY BOWEL DISEASER01DK042191 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI COMINELLI, FABIO, PIZARRO, THERESA TORRES · 1995 to 2022
$4.7M
Innate Immune Signal Transduction Specificity in Inflammatory DiseaseR01GM086550 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI ABBOTT, DEREK W · 2009 to 2020
$3.8M
CYTOKINES AND INFLAMMATORY BOWEL DISEASER37DK042191 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI COMINELLI, FABIO · 1999 to 2009
$3.8M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
The pathogenic roles of GSDMD-dependent gut epithelium extracellular vesicles in IBDR01DK125293 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Theresa Torres Pizarro · 2021 to 2026
$3.3M
An organotypic model recapitulating colon cancer microenvironment and metastasisU01CA214300 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HUANG, EMINA HUI-NA, SHEN, XILING · 2017 to 2021
$3.1M
Innate Immune Signal Transduction Specificity in Inflammatory DiseaseR35GM141603 · NIGMS · NATIONAL JEWISH HEALTH · PI Derek W Abbott · 2021 to 2026
$1.9M
Actomyosin cytoskeleton and the regulation of intestinal eipithelial barrierR01DK108278 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI IVANOV, ANDREI IVANOVICH · 2016 to 2019
$1.4M
Medical Research Council MC_PC_MR/S025952/1Medical Research Council MC_UU_00008/7Medical Research Council MC_UU_12010/7Medical Research Council MR/S036377/1NCI NIH HHS U01 CA214300NIAID NIH HHS P01 AI141350NIAID NIH HHS T32 AI089474NIDDK NIH HHS P01 DK091222NIDDK NIH HHS P30 DK097948NIDDK NIH HHS R01 DK042191NIDDK NIH HHS R01 DK108278NIDDK NIH HHS R01 DK125293NIDDK NIH HHS R01 DK126702NIDDK NIH HHS R37 DK042191NIDDK NIH HHS R56 DK042191NIDDK NIH HHS T35 DK111373NIGMS NIH HHS R01 GM086550NIGMS NIH HHS R35 GM141603NIGMS NIH HHS T32 GM007250NIH HHS S10 OD016164
6 · The paper itself

Abstract

Gasdermins are a family of structurally related proteins originally described for their role in pyroptosis. Gasdermin B (GSDMB) is currently the least studied, and while its association with genetic susceptibility to chronic mucosal inflammatory disorders is well established, little is known about its functional relevance during active disease states. Herein, we report increased GSDMB in inflammatory bowel disease, with single-cell analysis identifying epithelial specificity to inflamed colonocytes/crypt top colonocytes. Surprisingly, mechanistic experiments and transcriptome profiling reveal lack of inherent GSDMB-dependent pyroptosis in activated epithelial cells and organoids but instead point to increased proliferation and migration during in vitro wound closure, which arrests in GSDMB-deficient cells that display hyper-adhesiveness and enhanced formation of vinculin-based focal adhesions dependent on PDGF-A-mediated FAK phosphorylation. Importantly, carriage of disease-associated GSDMB SNPs confers functional defects, disrupting epithelial restitution/repair, which, altogether, establishes GSDMB as a critical factor for restoration of epithelial barrier function and the resolution of inflammation.

Indexed as

PyroptosisBase SequenceCase-Control StudiesCell AdhesionCell MembraneCell MovementCell ProliferationEpithelial CellsFocal Adhesion Protein-Tyrosine KinasesGasderminsHEK293 CellsHT29 CellsHumansInflammatory Bowel DiseasesMethotrexateMutationFocal Adhesion Protein-Tyrosine KinasesGasderminsGSDMB protein, humanMethotrexatePore Forming Cytotoxic Proteinsepithelial organoidsepithelial restitution and repairFAKfocal adhesion kinasegasdermin BgasderminsGSDMBGSDMB genetic polymorphismsinflammatory bowel diseaseintestinal epithelial cellsmethotrexateMtxPDGFAplatelet-derived growth factor Aresolution of inflammationsingle-cell profilingsingle-cell RNA-seq

Identifiers

PMID35021065
PMCPMC8879997
OpenAlexW4206183937

What OpenQuestion holds

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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.