Evidence map›Paper›PMID 34302470›Full record

ArticleInflammatory bowel diseases2022

Effect of ABT-263 on Intestinal Fibrosis in Human Myofibroblasts, Human Intestinal Organoids, and the Mouse Salmonella typhimurium Model.

Laura A Johnson, Eva S Rodansky, Anhdao Tran, Stephen G Collins, Kathryn A Eaton, Benjamin Malamet, Calen A Steiner, Sha Huang, Jason R Spence, Peter D R Higgins

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Intestinal strictures in Crohn's disease: a 2021 update.Therapeutic advances in gastroenterology · 2022
    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

10 authors at 1 institution in 1 country.

Laura A JohnsonDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-3338-8315
Eva S RodanskyDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Anhdao TranDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Stephen G CollinsDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Kathryn A EatonDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
Benjamin MalametDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Calen A SteinerDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Sha HuangDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Peter D R HigginsDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
University of Michigan · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Training in Basic and Translational Digestive SciencesT32DK094775 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHN Y KAO, LINDA C. SAMUELSON · 2012 to 2026
$3.6M
Nonlinear Ultrasound: an Imaging Biomarker of Intestinal Fibrosis in Crohn's DiseaseR01DK109032 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DILLMAN, JONATHAN RUSSELL, HIGGINS, PETER D.R. · 2016 to 2019
$2.4M
NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK109032NIDDK NIH HHS T32 DK094775
6 · The paper itself

Abstract

backgroundIntestinal fibrosis and subsequent intestinal obstruction are common complications of Crohn's disease (CD). Current therapeutics combat inflammation, but no pharmacological therapy exists for fibrostenotic disease. Pathological persistence of activated intestinal myofibroblasts is a key driver of fibrosis in CD. In other organ systems, BH-3 mimetic drugs that affect Bcl-2 apoptotic pathways induce apoptosis in activated myofibroblasts and reduce fibrogenic gene expression, thereby reducing fibrosis.

methodsWe evaluated the proapoptotic and antifibrotic efficacy of several classes of BH-3 mimetics in 2 in vitro fibrogenesis models. The candidate molecule, ABT-263, was advanced to a 3-dimensional human intestinal organoid (HIO) model. Finally, the therapeutic efficacy of ABT-263 was evaluated in the mouse Salmonella typhimurium intestinal fibrosis model.

resultsThe BH-3 mimetics induced apoptosis, repressed fibrotic protein expression, and reduced fibrogenic gene expression in normal human intestinal myofibroblasts. The BH-3 mimetics that target Bcl-2 and Bcl-xl demonstrated the greatest efficacy in vitro. The ABT-199 and ABT-263 induced apoptosis and ameliorated fibrogenesis in the in vitro myofibroblast models. In the HIO model, ABT-263 inhibited fibrogenesis and induced apoptosis. In the mouse S. typhimurium model, dose-dependent reduction in macroscopic pathology, histological inflammation, inflammatory and fibrotic gene expression, and extracellular matrix protein expression indicated ABT-263 may reduce intestinal fibrosis.

conclusionsIn vitro, the antifibrotic efficacy of BH-3 mimetics identifies the Bcl-2 pathway as a druggable target and BH-3 mimetics as putative therapeutics. Reduction of inflammation and fibrosis in the mouse intestinal fibrosis model by ABT-263 indicates BH-3 mimetics as potential, novel antifibrotic therapeutics for Crohn's disease.

Indexed as

MyofibroblastsSalmonella typhimuriumAniline CompoundsAnimalsFibrosisHumansMiceOrganoidsSulfonamidesAniline CompoundsnavitoclaxSulfonamidesABT-263Bcl-2BH-3 mimeticCrohn’s diseasefibrosisinflammatory bowel diseasemyofibroblastnavitoclax

Identifiers

PMID34302470
PMCPMC9017142
OpenAlexW3184114069

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.