ArticleInvestigative ophthalmology & visual science2014
The role of endogenous epidermal growth factor receptor ligands in mediating corneal epithelial homeostasis.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- 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 · 2026Article
- Apicobasal Polarity Protein PARD3 Plays an Essential Role in Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- Mpox Virus and its ocular surface manifestations.The ocular surface · 2024Review
- Elucidating the mechanism of corneal epithelial cell repair: unraveling the impact of growth factors.Frontiers in medicine · 2024Review
- Review
- Knockout of c-Cbl/Cbl-b slows c-Met trafficking resulting in enhanced signaling in corneal epithelial cells.The Journal of biological chemistry · 2023Article
- Schwann Cells Are Key Regulators of Corneal Epithelial Renewal.Investigative ophthalmology & visual science · 2023Article
- Innate Immune System Activation, Inflammation and Corneal Wound Healing.International journal of molecular sciences · 2022Review
- Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats.Frontiers in pharmacology · 2022Article
- Review
- Burst of Corneal Dendritic Cells during Trastuzumab and Paclitaxel Treatment.Diagnostics (Basel, Switzerland) · 2021Article
- Knockout of c-Cbl slows EGFR endocytic trafficking and enhances EGFR signaling despite incompletely blocking receptor ubiquitylation.Pharmacology research & perspectives · 2021Article
- Review
- Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration.Frontiers in pharmacology · 2021Article
- High ErbB3 activating activity in human blood is not due to circulating neuregulin-1 beta.Life sciences · 2020Article
- Epidermal Growth Factor Stimulates Transforming Growth Factor-Beta Receptor Type II Expression In Corneal Epithelial Cells.Scientific reports · 2019Article
- Betacellulin (BTC) Biases the EGFR To Dimerize with ErbB3.Molecular pharmacology · 2018Article
- Role of IL-18 induced Amphiregulin expression on virus induced ocular lesions.Mucosal immunology · 2018Article
- Corneal Nerve Fiber Structure, Its Role in Corneal Function, and Its Changes in Corneal Diseases.BioMed research international · 2017Review
- Administration of Menadione, Vitamin K3, Ameliorates Off-Target Effects on Corneal Epithelial Wound Healing Due to Receptor Tyrosine Kinase Inhibition.Investigative ophthalmology & visual science · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo provide a comprehensive study of the biological role and therapeutic potential of six endogenous epidermal growth factor receptor (EGFR) ligands in corneal epithelial homeostasis.
methodsKinetic analysis and dose response curves were performed by using in vitro and in vivo wound-healing assays. Biochemical assays were used to determine receptor expression and activity. Human tears were collected and quantitatively analyzed by multianalyte profiling for endogenous EGFR ligands.
resultsEpidermal growth factor receptor ligands improved wound closure and activated EGFR, but betacellulin (BTC) was the most efficacious promoter of wound healing in vitro. In contrast, only epidermal growth factor (EGF) promoted wound healing in vivo. Human tears from 25 healthy individuals showed EGFR ligands at these average concentrations: EGF at 2053 ± 312.4 pg/mL, BTC at 207 ± 39.4 pg/mL, heparin-binding EGF at 44 ± 5.8 pg/mL, amphiregulin at 509 ± 28.8 pg/mL, transforming growth factor-α at 84 ± 19 pg/mL, and epiregulin at 52 ± 15 pg/mL.
conclusionsUnder unwounded conditions, only EGF was present at concentrations near the ligand's Kd for the receptor, indicating it is the primary mediator of corneal epithelial homeostasis. Other ligands were present but at concentrations 11- to 7500-fold less their Kd, preventing significant ligand binding. Further, the high levels of EGF and its predicted binding preclude receptor occupancy by exogenous ligand and can explain the discrepancy between the in vitro and in vivo data. Therefore, therapeutic use of EGFR ligands may be unpredictable and impractical.
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Registered trials
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.