Evidence map›Paper›PMID 22095949›Full record

ArticleJournal of the American Society of Nephrology : JASN2012

EGFR signaling promotes TGFβ-dependent renal fibrosis.

Jianchun Chen, Jian-Kang Chen, Kojiro Nagai, David Plieth, Mingqi Tan, Tang-Cheng Lee, David W Threadgill, Eric G Neilson, Raymond C Harris

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

181 citing papers in PubMed, 1 synthesis or guideline pooled it, 291 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. The roles of free-fatty acid receptors in the pathophysiology of renal disorders.The Journal of pharmacology and experimental therapeutics · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Mechanism ofRenal failure · 2025
    Article
  14. Article
  15. D-glucuronyl C5-Epimerase Binds to EGFR to Suppress Kidney Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

121 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Jianchun ChenDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Jian-Kang Chen
Kojiro Nagai
David Plieth
Mingqi Tan
Tang-Cheng Lee
David W Threadgill
Eric G Neilson
Raymond C Harris
North Carolina State University · USVanderbilt University · USVanderbilt University Medical Center · US

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
TRANSPORT EFFECTS OF ARACHIDONATE METABOLITES IN PERFUSED TUBULEP01DK038226 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROWN, NANCY J. · 1986 to 2015
$22.1M
The Role of the EGF Receptor in Acute and Chronic Renal InjuryR01DK051265 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RAYMOND C. HARRIS, Mingzhi Zhang · 1997 to 2026
$10.1M
The role of the innate immune cell cyclooxygenase/prostaglandin system in blood pressureregulationR01DK062794 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RAYMOND C. HARRIS, Mingzhi Zhang · 2003 to 2026
$9.4M
Vanderbilt O'Brien Mouse Kidney Physiology and Disease CenterP30DK079341 · NIDDK · VANDERBILT UNIVERSITY · PI HARRIS, RAYMOND C. · 2008 to 2013
$4.4M
ERBB receptors in normal and cancerous colon biologyR01CA092479 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI THREADGILL, DAVID W. · 2001 to 2012
$2.8M
RESPONSE OF RENAL CELLS IN INTERSTITIAL NEPHRITISR01DK046282 · NIDDK · VANDERBILT UNIVERSITY · PI NEILSON, ERIC GRANT · 1993 to 2007
$2.5M
Mechanism of Compensatory Renal HypertrophyR01DK083575 · NIDDK · VANDERBILT UNIVERSITY · PI CHEN, JIAN-KANG · 2011 to 2015
$1.7M
NCI NIH HHS CA092479NCI NIH HHS R01 CA092479NIDDK NIH HHS DK38226NIDDK NIH HHS DK46282NIDDK NIH HHS DK51265NIDDK NIH HHS DK62794NIDDK NIH HHS DK79341NIDDK NIH HHS DK83575NIDDK NIH HHS P01 DK038226NIDDK NIH HHS P30 DK079341NIDDK NIH HHS R01 DK046282NIDDK NIH HHS R01 DK051265NIDDK NIH HHS R01 DK062794NIDDK NIH HHS R01 DK083575NIEHS NIH HHS P30 ES010126
6 · The paper itself

Abstract

The mechanisms by which angiotensin II (Ang II) promotes renal fibrosis remain incompletely understood. Ang II both stimulates TGFβ signaling and activates the EGF receptor (EGFR), but the relative contribution of these pathways to renal fibrogenesis is unknown. Using a murine model with EGFR-deficient proximal tubules, we demonstrate that upstream activation of EGFR-dependent ERK signaling is critical for mediating sustained TGFβ expression in renal fibrosis. Persistent activation of the Ang II receptor stimulated ROS-dependent phosphorylation of Src, leading to sustained EGFR-dependent signaling for TGFβ expression. Either genetic or pharmacologic inhibition of EGFR significantly decreased TGFβ-mediated fibrogenesis. We conclude that TGFβ-mediated tissue fibrosis relies on a persistent feed-forward mechanism of EGFR/ERK activation through an unexpected signaling pathway, highlighting EGFR as a potential therapeutic target for modulating tissue fibrogenesis.

Indexed as

Angiotensin IIAnimalsErbB ReceptorsExtracellular Signal-Regulated MAP KinasesFibrosisKidneyLLC-PK1 CellsMaleMiceMice, Inbred BALB CPhosphorylationReactive Oxygen SpeciesSignal TransductionSmad2 ProteinSmad3 ProteinSwineAngiotensin IIEGFR protein, mouseErbB ReceptorsExtracellular Signal-Regulated MAP KinasesReactive Oxygen SpeciesSmad2 ProteinSmad2 protein, mouseSmad3 ProteinSmad3 protein, mouseTransforming Growth Factor beta

Identifiers

PMID22095949
PMCPMC3269185
OpenAlexW2169981609

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.