Evidence map›Paper›PMID 32492075›Full record

ArticlePloS one2020

Pharmacological inhibition of P2RX7 ameliorates liver injury by reducing inflammation and fibrosis.

Bernat Baeza-Raja, Andrew Goodyear, Xiao Liu, Kevin Lam, Lynn Yamamoto, Yingwu Li, G Steven Dodson, Toshi Takeuchi, Tatiana Kisseleva, David A Brenner and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

35 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Human Hepatic Stellate Cells: Isolation and Characterization.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  20. Emerging Role of NLRP3 Inflammasome and Pyroptosis in Liver Transplantation.International journal of molecular sciences · 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

11 authors at 2 institutions in 1 country.

Bernat Baeza-RajaSecond Genome Inc., South San Francisco, California, United States of America.ORCID 0000-0003-4458-3079
Andrew GoodyearSecond Genome Inc., South San Francisco, California, United States of America.
Xiao LiuDepartment of Surgery, University of California San Diego, La Jolla, California, United States of America.
Kevin LamDepartment of Surgery, University of California San Diego, La Jolla, California, United States of America.
Lynn YamamotoSecond Genome Inc., South San Francisco, California, United States of America.
Yingwu LiSecond Genome Inc., South San Francisco, California, United States of America.
G Steven DodsonSecond Genome Inc., South San Francisco, California, United States of America.
Toshi TakeuchiSecond Genome Inc., South San Francisco, California, United States of America.
Tatiana KisselevaDepartment of Surgery, University of California San Diego, La Jolla, California, United States of America.
David A BrennerDepartment of Medicine, University of California San Diego, La Jolla, California, United States of America.
Karim DabbaghSecond Genome Inc., South San Francisco, California, United States of America.
Second Genome (United States) · USUniversity of California San Diego · US

Funding

The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HIDEKAZU TSUKAMOTO · 1999 to 2026
$45.8M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
The Role of IL-17 in Alcoholic Liver Disease and CancerU01AA022614 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL, KISSELEVA, TATIANA · 2014 to 2018
$1.8M
NIAAA NIH HHS P50 AA011999NIAAA NIH HHS U01 AA022614NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101737
6 · The paper itself

Abstract

Extracellular adenosine triphosphate (eATP) released by damaged cells, and its purinergic receptors, comprise a crucial signaling network after injury. Purinergic receptor P2X7 (P2RX7), a major driver of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and IL-1β processing, has been shown to play a role in liver injury in murine diet- and chemically-induced liver injury models. It is unclear, however, whether P2RX7 plays a role in non-alcoholic steatohepatitis (NASH) and which cell type is the main target of P2RX7 pharmacological inhibition. Here, we report that P2RX7 is expressed by infiltrating monocytes and resident Kupffer cells in livers from NASH-affected individuals. Using primary isolated human cells, we demonstrate that P2RX7 expression in CD14+ monocytes and Kupffer cells primarily mediates IL-1β release. In addition, we show that pharmacological inhibition of P2RX7 in monocytes and Kupffer cells, blocks IL-1β release, reducing hepatocyte caspase 3/7 activity, IL-1β-mediated CCL2 and CCL5 chemokine gene expression and secretion, and hepatic stellate cell (HSC) procollagen secretion. Consequently, in a chemically-induced nonhuman primate model of liver fibrosis, treatment with a P2RX7 inhibitor improved histological characteristics of NASH, protecting from liver inflammation and fibrosis. Taken together, these findings underscore the critical role of P2RX7 in the pathogenesis of NASH and implicate P2RX7 as a promising therapeutic target for the management of this disease.

Indexed as

AnimalsCaspase 3Cells, CulturedChemokine CCL2Hepatic Stellate CellsHepatocytesHumansInflammationInterleukin-1betaKupffer CellsLipopolysaccharidesLiverLiver CirrhosisMacaca fascicularisMaleMonocytesCaspase 3Chemokine CCL2Interleukin-1betaLipopolysaccharidesP2RX7 protein, humanProcollagenPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7

Identifiers

PMID32492075
PMCPMC7269334
OpenAlexW3030440221

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.