Evidence map›Paper›PMID 21677150›Full record

ArticleAmerican journal of physiology. Renal physiology2011

ERK pathway mediates P2X7 expression and cell death in renal interstitial fibroblasts exposed to necrotic renal epithelial cells.

Murugavel Ponnusamy, Na Liu, Rujun Gong, Haidong Yan, Shougang Zhuang

Abstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. The dark side of extracellular ATP in kidney diseases.Journal of the American Society of Nephrology : JASN · 2015
    Review
  10. P2X7 receptor inhibition protects against ischemic acute kidney injury in mice.American journal of physiology. Cell physiology · 2015
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
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

5 authors at 3 institutions in 2 countries.

Murugavel PonnusamyDepartment of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, USA.
Na Liu
Rujun Gong
Haidong Yan
Shougang Zhuang
Rhode Island Hospital · USShanghai East Hospital · CNBrown University · US

Funding

Histone deacetylases as novel therapeutic targets for kidney fibrosisR01DK085065 · NIDDK · RHODE ISLAND HOSPITAL · PI ZHUANG, SHOUGANG · 2010 to 2017
$2.8M
Dedifferentiation Following Renal Cell InjuryR01DK071997 · NIDDK · RHODE ISLAND HOSPITAL · PI ZHUANG, SHOUGANG · 2006 to 2009
$1.1M
NIDDK NIH HHS DK-071997NIDDK NIH HHS DK-085065NIDDK NIH HHS R01 DK085065
6 · The paper itself

Abstract

We recently reported that necrotic renal proximal epithelial cells (RPTC) stimulate the expression of P2X7 receptor in renal fibroblasts and that P2X7 receptor mediates deleterious epithelial-fibroblast cross talk. The present study was carried out to investigate the signaling mechanism of necrotic RPTC-induced P2X7 expression in cultured renal interstitial fibroblasts (NRK-49F). Exposure of NRK-49F to necrotic RPTC supernatant (RPTC-Sup) induced a time- and dose-dependent phosphorylation of several signaling pathways including extracellular signal-regulated kinases (ERK1/2), p38, c-Jun N-terminal kinases (JNKs), and AKT in NRK-49F. Pharmacological inhibition of ERK1/2, but not p38, JNK, and AKT pathways, blocked RPTC-Sup-induced P2X7 expression and renal interstitial fibroblast death. Knockdown of ERK1/2 or MEK1, a direct upstream activator of ERK1/2, also reduced RPTC-Sup-induced P2X7 expression and cell death of renal fibroblasts. Conversely, overexpression of MEK1 enhanced these responses. Upon necrotic RPTC exposure, phosphorylation of Elk1, a transcriptional factor targeted by ERK1/2, was increased in NRK-49F, and knockdown of Elk1 by siRNA remarkably reduced RPTC-Sup-induced P2X7 expression as well as renal fibroblast death. Furthermore, silencing of MEK1 inhibited Elk1 phosphorylation in response to necrotic RPTC, whereas overexpression of MEK1 increased Elk1 phosphorylation. Taken together, these data reveal that necrotic RPTC induces P2X7 expression in renal fibroblasts through activation of the MEK1-ERK1/2-Elk1 signaling pathway.

Indexed as

AnimalsApoptosisCell CommunicationCell LineEpithelial Cellsets-Domain Protein Elk-1Extracellular Signal-Regulated MAP KinasesFibroblastsKidney Cortex NecrosisKidney Tubules, ProximalMAP Kinase Kinase 1MAP Kinase Kinase 4MiceModels, Animalp38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-aktElk1 protein, ratets-Domain Protein Elk-1Extracellular Signal-Regulated MAP KinasesMAP Kinase Kinase 1MAP Kinase Kinase 4p38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-aktReceptors, Purinergic P2X7RNA, Small Interfering

Identifiers

PMID21677150
PMCPMC3174556
OpenAlexW2144088689

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.