| Transactivation of EGFR mediates insulin-stimulated ERK1/2 activation and enhanced cell migration in human corneal epithelial cells. | |
| | |
MedLine Citation:
|
PMID: 17149366 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: Insulin activates phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK)-1/2 in human corneal epithelial cells. These events have been shown to be involved in wound healing. However, the mechanism of insulin-induced ERK pathway is not clear during corneal wound healing. In this study, the effect of insulin associated with epidermal growth factor receptor (EGFR) on wound healing in transformed human corneal epithelial cells was investigated to determine the signaling mechanism involved. METHODS: SV40-immortalized human corneal epithelial (THCE) cells were cultured on a diluted Matrigel matrix that resembled the basement membrane of the corneal epithelium. A wound was introduced with a micropipette tip, and closure of the scratch wound was photographed 12 h after exposure to insulin. Activation of EGFR was analyzed by immunoprecipitation, and cytoskeletal rearrangements were visualized with rhodamine-conjugated phalloidin. RESULTS: Exposure of corneal epithelial cells to insulin induced phosphorylation of EGFR. Inhibition of EGFR activation by AG1478 or the MMP inhibitor, GM6001, reduced phosphorylation of insulin-induced ERK in the presence of insulin and delayed wound closure. In addition, cells exposed to insulin contained stress fibers and their submembranous cortical actin was depleted. These effects were inhibited by AG1478. CONCLUSIONS: Inhibition of EGFR activity decreases cell migration involved in insulin-induced wound repair, an effect that mimics inhibition of MMP activation. Inhibition of MMP activity leads to decreased EGFR phosphorylation. Our data show that insulin stimulates wound healing in the corneal epithelium by activating EGFR, and point to a novel insulin signaling pathway that acts during corneal wound healing. |
| | |
Authors:
|
Jungmook Lyu; Kyung-Suk Lee; Choun-Ki Joo |
Related Documents
:
|
1380456 - Phosphatidylinositol 3'-kinase is activated by association with irs-1 during insulin st... 9698376 - Partial activation of the insulin receptor kinase domain by juxtamembrane autophosphory... 15913956 - Caveolin; different roles for insulin signal? 8770036 - Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways ... 22500736 - Blm helicase ortholog sgs1 is a central regulator of meiotic recombination intermediate... 11375126 - Mitogenic activity of high molecular weight forms of insulin-like growth factor-ii in a... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-11-16 |
Journal Detail:
|
Title: Molecular vision Volume: 12 ISSN: 1090-0535 ISO Abbreviation: Mol. Vis. Publication Date: 2006 |
Date Detail:
|
Created Date: 2006-12-06 Completed Date: 2007-01-16 Revised Date: 2013-06-03 |
Medline Journal Info:
|
Nlm Unique ID: 9605351 Medline TA: Mol Vis Country: United States |
Other Details:
|
Languages: eng Pagination: 1403-10 Citation Subset: IM |
Affiliation:
|
Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Line, Transformed Cell Movement / drug effects Cytoskeleton / ultrastructure Dipeptides / pharmacology Enzyme Activation Epithelium, Corneal / drug effects, injuries*, pathology, physiopathology* Extracellular Signal-Regulated MAP Kinases / metabolism* Humans Insulin / pharmacology* Isoenzymes / metabolism Metalloendopeptidases / antagonists & inhibitors Phosphatidylinositol 3-Kinases / metabolism Phosphorylation / drug effects Protease Inhibitors / pharmacology Quinazolines Receptor, Epidermal Growth Factor / antagonists & inhibitors, genetics* Transcriptional Activation* Tyrphostins / pharmacology Wound Healing* |
| Chemical | |
Reg. No./Substance:
|
0/Dipeptides; 0/Insulin; 0/Isoenzymes; 0/N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; 0/Protease Inhibitors; 0/Quinazolines; 0/Tyrphostins; 170449-18-0/tyrphostin AG 1478; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.4.24.-/Metalloendopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: In vivo confocal microscopy and ex vivo flow cytometry: new tools for assessing ocular inflammation ...
Next Document: Hypermethylation of the p16 gene promoter in pterygia and its association with the expression of DNA...