Evidence map›Paper›PMID 24985478›Full record

ArticleInvestigative ophthalmology & visual science2014

Antagonizing c-Cbl enhances EGFR-dependent corneal epithelial homeostasis.

Jamie S Rush, Michael A Boeving, William L Berry, Brian P Ceresa

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

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. A c-Cbl/Cbl-b antagonist inhibits EGFR ubiquitylation and sustains EGFR phosphorylation to enhance corneal re-epithelialization.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Article
  5. Article
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  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Progress in corneal wound healing.Progress in retinal and eye research · 2015
    Review
  13. 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

4 authors at 2 institutions in 1 country.

Jamie S RushDepartment of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, United States.
Michael A BoevingDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, United States.
William L BerryDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, United States.
Brian P CeresaDepartment of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, United States Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma, United States.
University of Oklahoma Health Sciences Center · USUniversity of Louisville · US

Funding

Modulation of EGFR Signaling to Promote Corneal Epithelial Wound HealingR01EY021497 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CERESA, BRIAN P. · 2012 to 2014
$1.0M
Regulation of EGFR Signaling by the Endocytic PathwayR01GM092874 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CERESA, BRIAN P. · 2010 to 2013
$883k
NEI NIH HHS 1R01EY021497-01NEI NIH HHS R01 EY021497NIGMS NIH HHS 1R01GM092874-01A1NIGMS NIH HHS R01 GM092874
6 · The paper itself

Abstract

purposeIn many cell types, the E3 ubiquitin ligase, c-Cbl, induces ligand-dependent ubiquitylation of the epidermal growth factor receptor (EGFR) and targets the receptor for lysosomal degradation. The goal of this study was to determine whether c-Cbl is a negative regulator of EGFR in the corneal epithelium and if it can be inhibited to promote corneal epithelial homeostasis.

methodsExpression and activity of c-Cbl were blocked in immortalized human corneal epithelial cells (hTCEpi) using RNAi and pharmacological agents ([4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo-d-3,4-pyrimidine] or PP1). Following c-Cbl inhibition, cells were assessed for ligand-dependent receptor ubiquitylation, receptor phosphorylation, and in vitro wound healing. Subsequent experiments used PP1 in hTCEpi cells and monitored in vivo murine corneal epithelial wound healing.

resultsKnockdown and inhibition of c-Cbl decreased ligand-dependent ubiquitylation of the EGFR and prolonged receptor activity as measured by tyrosine phosphorylation. Further, these treatments also increased the extent of ligand-dependent corneal epithelial wound healing in vitro and in vivo.

conclusionManipulating the duration of EGFR activity can enhance the rate of restoration of the corneal epithelial layer. Based on our findings, c-Cbl is a new therapeutic target to enhance EGFR-mediated corneal epithelial homeostasis that bypasses the limitations of previous approaches.

Indexed as

AnimalsCells, CulturedDisease Models, AnimalEnzyme InhibitorsEnzyme-Linked Immunosorbent AssayEpithelium, CornealErbB ReceptorsEye InjuriesFemaleHomeostasisHumansImmunoblottingMiceMice, Inbred C57BLPhosphorylationProto-Oncogene Proteins c-cbl4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidineCbl protein, mouseEnzyme InhibitorsErbB ReceptorsProto-Oncogene Proteins c-cblPyrazolesPyrimidinessrc-Family Kinasescorneal epitheliumcorneal wound healingEGFRendocytic trafficking

Identifiers

PMID24985478
PMCPMC4120408
OpenAlexW2051919508

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.