Document Detail


ERK/p44p42 mitogen-activated protein kinase mediates EGF-stimulated proliferation of conjunctival goblet cells in culture.
MedLine Citation:
PMID:  18421078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To determine whether activation of the ERK pathway by EGF leads to rat and human goblet cell proliferation.
METHODS: The conjunctiva was removed from male Sprague-Dawley rats. Human conjunctiva was removed during ocular surgery. The tissue was minced and goblet cells were grown. The cells were stimulated with EGF (10(-7) M) for 1 and 5 minutes and Western blot analysis was performed with an antibody against phosphorylated EGFR, to measure the activation of the EGF receptor (EGFR). The cells were incubated with EGF (10(-7) M) for 24 hours, and cell proliferation was measured by WST-8. Inhibitors were added either 20 minutes before EGF or 2 hours after. The cells were stimulated with EGF (10(-7) M) for 1 minute to 24 hours. The number of cells expressing phosphorylated ERK (pERK) in the nucleus and Ki-67 was determined by immunofluorescence.
RESULTS: EGF increased the activation of EGFR in rat conjunctival goblet cells. EGF-stimulated proliferation was inhibited by the EGFR inhibitor AG1478 and the MEK inhibitor U0126 in rat and human cultured goblet cells. EGF caused the translocation of pERK to the nucleus in a biphasic manner. Inhibition of the second peak with U0126 prevented proliferation. EGF-stimulated goblet cells progressed through the cell cycle expressing pERK in the nucleus.
CONCLUSIONS: EGF stimulated human and rat conjunctival goblet cell proliferation by activating the EGFR. EGFR stimulated ERK causing its biphasic translocation to the nucleus. The second peak response is responsible for cell proliferation, but the role of the first peak is not known.
Authors:
Marie A Shatos; Jian Gu; Robin R Hodges; Kameran Lashkari; Darlene A Dartt
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-04-17
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  49     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-08-12     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3351-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Animals
Blotting, Western
Cell Proliferation / drug effects*
Cells, Cultured
Conjunctiva / cytology
Epidermal Growth Factor / pharmacology*
Female
Fluorescent Antibody Technique, Indirect
Goblet Cells / cytology*,  metabolism
Humans
Ki-67 Antigen / metabolism
Male
Middle Aged
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Phosphorylation
Protein Transport
Rats
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor / metabolism
Grant Support
ID/Acronym/Agency:
EY09577/EY/NEI NIH HHS; R01 EY009057/EY/NEI NIH HHS; R01 EY009057-12/EY/NEI NIH HHS; R01 EY009057-13/EY/NEI NIH HHS; R01 EY019470/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Egfr protein, rat; 0/Ki-67 Antigen; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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