Evidence map›Paper›PMID 37030630›Full record

ArticleCellular and molecular gastroenterology and hepatology2023

PTPN2 Is a Critical Regulator of Ileal Paneth Cell Viability and Function in Mice.

Vinicius Canale, Marianne R Spalinger, Rocio Alvarez, Anica Sayoc-Becerra, Golshid Sanati, Salomon Manz, Pritha Chatterjee, Alina N Santos, Hillmin Lei, Sharon Jahng and 6 more

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

Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Ptpn2: A Critical Regulator of Paneth Cell Homeostasis.Cellular and molecular gastroenterology and hepatology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Vinicius CanaleDivision of Biomedical Sciences, University of California Riverside, Riverside, California; Biochemistry and Molecular Biology Department, University of California Riverside, Riverside, California; CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
Marianne R SpalingerDivision of Biomedical Sciences, University of California Riverside, Riverside, California; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Rocio AlvarezDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Anica Sayoc-BecerraDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Golshid SanatiDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Salomon ManzDivision of Biomedical Sciences, University of California Riverside, Riverside, California; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Pritha ChatterjeeDivision of Biomedical Sciences, University of California Riverside, Riverside, California; Biochemistry and Molecular Biology Department, University of California Riverside, Riverside, California.
Alina N SantosDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Hillmin LeiDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Sharon JahngDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Timothy ChuDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Ali ShawkiDivision of Biomedical Sciences, University of California Riverside, Riverside, California.
Elaine HansonDivision of Gastroenterology, University of California, San Diego, La Jolla, California.
Lars EckmannDivision of Gastroenterology, University of California, San Diego, La Jolla, California.
André J OuelletteDepartment of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
Declan F McColeDivision of Biomedical Sciences, University of California Riverside, Riverside, California. Electronic address: declan.mccole@ucr.edu.
University of California, Riverside · USUniversity Hospital of Zurich · CHUniversity of California San Diego · USUniversity of Southern California · US

Funding

San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LARS ECKMANN, Bernd G. Schnabl · 2019 to 2026
$10.8M
A NOVEL ROLE FOR PTPN2 IN INTESTINAL EPITHELIAL BARRIER REGULATIONR01DK091281 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Declan McCole · 2012 to 2026
$5.5M
Tyrosine Phosphatase Regulation of Mucosal Macrophage-Epithelial Cell Cross-talkR01AI153314 · NIAID · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MCCOLE, DECLAN · 2020 to 2024
$2.5M
Mechanistic Characterization of the IBD Risk Gene, PTPN2, as a Novel Susceptibility Marker for Increased SARS-CoV-2 InfectionR01DK130373 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MCCOLE, DECLAN · 2021 to 2023
$1.1M
Inflammatory Bowel Disease Susceptibility Gene Regulation of AnemiaR21AI152017 · NIAID · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MCCOLE, DECLAN · 2021 to 2022
$428k
NIAID NIH HHS R01 AI153314NIAID NIH HHS R21 AI152017NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK091281NIDDK NIH HHS R01 DK130373
6 · The paper itself

Abstract

BACKGROUND &

aimsLoss-of-function variants in the PTPN2 gene are associated with increased risk of inflammatory bowel disease. We recently showed that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice, restricting expansion of a small intestinal pathobiont associated with inflammatory bowel disease. Here, we aimed to identify how Ptpn2 loss affects ileal IEC subtypes and their function in vivo.

methodsConstitutive Ptpn2 wild-type, heterozygous, and knockout (KO) mice, as well as mice with inducible deletion of Ptpn2 in IECs, were used in the study. Investigation was performed using imaging techniques, flow cytometry, enteroid culture, and analysis of gene and protein levels of IEC markers.

resultsPartial transcriptome analysis showed that expression of Paneth cell-associated antimicrobial peptides Lyz1, Pla2g2a, and Defa6 was down-regulated markedly in Ptpn2-KO mice compared with wild-type and heterozygous. In parallel, Paneth cell numbers were reduced, their endoplasmic reticulum architecture was disrupted, and the endoplasmic reticulum stress protein, C/EBP-homologous protein (CHOP), was increased in Ptpn2-KO mice. Despite reduced Paneth cell number, flow cytometry showed increased expression of the Paneth cell-stimulatory cytokines interleukin 22 and interferon γ

conclusionsConstitutive Ptpn2 deficiency affects Paneth cell viability and compromises Paneth cell-specific antimicrobial peptide production. The observed effects may contribute to the increased susceptibility to intestinal infection and dysbiosis in these mice.

Indexed as

Inflammatory Bowel DiseasesPaneth CellsAnimalsCell SurvivalIleumMiceMice, KnockoutProtein Tyrosine Phosphatase, Non-Receptor Type 2Protein Tyrosine Phosphatase, Non-Receptor Type 2Ptpn2 protein, mouseAntimicrobial PeptidesInflammatory Bowel DiseaseIntestinal Epithelial CellsLysozymeMicrobiomeTCPTP

Identifiers

PMID37030630
PMCPMC10213106
OpenAlexW4362676544

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.