Document Detail


Wound-induced ATP release and EGF receptor activation in epithelial cells.
MedLine Citation:
PMID:  17284517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have shown previously that wounding of human corneal epithelial (HCE) cells resulted in epidermal growth factor receptor (EGFR) transactivation through ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF). However, the initial signal to trigger these signaling events in response to cell injury remains elusive. In the present study, we investigated the role of ATP released from the injured cells in EGFR transactivation in HCE cells as well as in BEAS 2B cells, a bronchial epithelial cell line. Wounding of epithelial monolayer resulted in the release of ATP into the culture medium. The wound-induced rapid activation of phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) pathways in HCE cells was attenuated by eliminating extracellular ATP, ADP and adenosine. The nonhydrolyzable ATP analog ATP-gamma-S induced rapid and sustained EGFR activation that depended on HB-EGF shedding and ADAM (a disintegrin and metalloproteinase). Targeting pathways leading to HB-EGF shedding and EGFR activation attenuated ATP-gamma-S-enhanced closure of small scratch wounds. The purinoceptor antagonist reactive blue 2 decreased wound closure and attenuated ATP-gamma-S induced HB-EGF shedding. Taken together, our data suggest that ATP, released upon epithelial injury, acts as an early signal to trigger cell responses including an increase in HB-EGF shedding, subsequent EGFR transactivation and its downstream signaling, resulting in wound healing.
Authors:
Jia Yin; Keping Xu; Jing Zhang; Ashok Kumar; Fu-Shin X Yu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-02-06
Journal Detail:
Title:  Journal of cell science     Volume:  120     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-22     Completed Date:  2007-07-31     Revised Date:  2010-12-03    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  815-25     Citation Subset:  IM    
Affiliation:
Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, 4717 St Antoine Blvd, Detroit, MI 48201, USA.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / pharmacology
Adenosine Diphosphate / metabolism
Adenosine Triphosphate / analogs & derivatives,  pharmacology,  secretion*
Blotting, Western
Calcium / metabolism
Cell Line
Epidermal Growth Factor / metabolism
Epithelial Cells / cytology,  drug effects,  metabolism*
Extracellular Signal-Regulated MAP Kinases / metabolism
Fluorescent Antibody Technique
Humans
Intercellular Signaling Peptides and Proteins
Mitogen-Activated Protein Kinases / metabolism
Models, Biological
Phosphorylation / drug effects
Purinergic P2 Receptor Antagonists
Receptor, Epidermal Growth Factor / metabolism*
Signal Transduction / drug effects
Stress, Mechanical
Grant Support
ID/Acronym/Agency:
R01 EY010869-12/EY/NEI NIH HHS; R01 EY014080-04/EY/NEI NIH HHS; R01-EY10869/EY/NEI NIH HHS; R01-EY14080/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/Purinergic P2 Receptor Antagonists; 149176-25-0/heparin-binding EGF-like growth factor; 35094-46-3/adenosine 5'-O-(3-thiotriphosphate); 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate; 62229-50-9/Epidermal Growth Factor; 7440-70-2/Calcium; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.24.-/ADAM Proteins
Comments/Corrections

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