Evidence map›Paper›PMID 32086866›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020

P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling.

Sang Jun Han, Marianna Lovaszi, Mihwa Kim, Vivette D'Agati, György Haskó, H Thomas Lee

Open access · bronzeAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Novel P2X4 Receptor Antagonist MRS4719 Improves Ischemia/reperfusion Injury in Mice.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
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  15. Highly pathogenic coronaviruses and the kidney.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Review
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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

6 authors at 1 institution in 1 country.

Sang Jun HanDepartment of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Marianna LovasziDepartment of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Mihwa KimDepartment of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Vivette D'AgatiDepartment of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
György HaskóDepartment of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
H Thomas LeeDepartment of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Columbia University · US

Funding

Purinergic signaling in trauma and sepsisR01GM066189 · NIGMS · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI HASKO, GEORGE · 2002 to 2020
$4.7M
Purinergic signaling in granuloma-forming Th2 immunityR01DK113790 · NIDDK · RBHS-NEW JERSEY MEDICAL SCHOOL · PI GAUSE, WILLIAM CLARK, HASKO, GEORGE · 2017 to 2020
$1.9M
Paneth cells and acute kidney injuryR01DK109544 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LEE, H. THOMAS · 2017 to 2021
$1.8M
Peptidylarginine deiminase-4 and acute kidney injuryR01DK115694 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LEE, H. THOMAS · 2017 to 2021
$1.6M
NIDDK NIH HHS R01 DK109544NIDDK NIH HHS R01 DK113790NIDDK NIH HHS R01 DK115694NIGMS NIH HHS R01 GM066189
6 · The paper itself

Abstract

We tested the hypothesis that the P2X4 purinergic receptor (P2X4) exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular inflammation after ischemia and reperfusion (IR). Supporting this, P2X4-deficient (KO) mice were protected against ischemic AKI with significantly attenuated renal tubular necrosis, inflammation, and apoptosis when compared to P2X4 wild-type (WT) mice subjected to renal IR. Furthermore, WT mice treated with P2X4 allosteric agonist ivermectin had exacerbated renal IR injury whereas P2X4 WT mice treated with a selective P2X4 antagonist (5-BDBD) were protected against ischemic AKI. Mechanistically, induction of kidney NLRP3 inflammasome signaling after renal IR was significantly attenuated in P2X4 KO mice. A P2 agonist ATPγS increased NLRP3 inflammasome signaling (NLRP3 and caspase 1 induction and IL-1β processing) in isolated renal proximal tubule cells from WT mice whereas these increases were absent in renal proximal tubules isolated from P2X4 KO mice. Moreover, 5-BDBD attenuated ATPγS induced NLRP3 inflammasome induction in renal proximal tubules from WT mice. Finally, P2X4 agonist ivermectin induced NLRP3 inflammasome and pro-inflammatory cytokines in cultured human proximal tubule cells. Taken together, our studies suggest that renal proximal tubular P2X4 activation exacerbates ischemic AKI and promotes NLRP3 inflammasome signaling.

Indexed as

Acute Kidney InjuryAnimalsApoptosisCytokinesInflammasomesInflammationKidney Tubules, ProximalMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, Purinergic P2X4Reperfusion InjuryCytokinesInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, Purinergic P2X4apoptosisinflammasomeinflammationischemia and reperfusion injurynecrosisneutrophil

Identifiers

PMID32086866
PMCPMC7136150
OpenAlexW3007337192

What OpenQuestion holds

Textmetadata
LicenceTDM
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.