Document Detail

EGF and its related growth factors mediate sodium transport in mpkCCDc14 cells via ErbB2 (neu/HER-2) receptor.
MedLine Citation:
PMID:  20049896     Owner:  NLM     Status:  MEDLINE    
Amiloride-sensitive sodium entry, via the epithelial sodium channel (ENaC), is the rate-limiting step for Na(+) absorption. Epidermal growth factor (EGF) is involved in the regulation of Na(+) transport and ENaC activity. However it is still controversial exactly how EGF regulates ENaC and Na(+) absorption. The aim of the present study was to characterize the EGF regulation of Na(+) transport in cultured mouse renal collecting duct principal mpkCCD(c14) cells, a highly differentiated cell line which retains many characteristics of the cortical collecting duct (CCD). EGF dose dependently regulates basal transepithelial Na(+) transport in two phases: an acute phase (<4 h) and a chronic phase (>8 h). Similar effects were observed with TGF-alpha, HB-EGF, and amphiregulin which also belong to the EGF-related peptide growth factor family. Inhibition of MEK1/2 by PD98059 or U0126 increased acute effects and disrupted chronic effects of EGF on Na(+) reabsorption. Inhibition of PI3-kinase with LY294002 abolished acute effect of EGF. As assessed by Western blotting, ErbB2 is the most predominant member of the ErbB family detected in mpkCCD(c14) cells. Immunohistochemistry analysis revealed localization of ErbB2 in the CCD in Sprague-Dawley rat kidneys. Both acute and long-term effects of EGF were abolished when cells were treated with tyrphostin AG-825 and ErbB2 inhibitor II, chemically dissimilar selective inhibitors of the ErbB2 receptor. Thus, we conclude that EGF and its related growth factors are important for maintaining transepithelial Na(+) transport and that EGF biphasically modulates sodium transport in mpkCCD(c14) cells via the ErbB2 receptor.
Vladislav Levchenko; Nadezhda N Zheleznova; Tengis S Pavlov; Alain Vandewalle; Patricia D Wilson; Alexander Staruschenko
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  223     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-03-08     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  252-9     Citation Subset:  IM    
Copyright Information:
J. Cell. Physiol. 223: 252-259, 2010. (c) 2009 Wiley-Liss, Inc.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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MeSH Terms
Amiloride / pharmacology
Benzothiazoles / pharmacology
Blotting, Western
Butadienes / pharmacology
Cell Line
Chromones / pharmacology
Dose-Response Relationship, Drug
Epidermal Growth Factor / metabolism*
Epithelial Sodium Channels / drug effects,  metabolism*
Flavonoids / pharmacology
Glycoproteins / antagonists & inhibitors,  metabolism*
Intercellular Signaling Peptides and Proteins / metabolism
Ion Transport
Kidney Tubules, Collecting / cytology,  drug effects,  metabolism*
MAP Kinase Kinase 1 / antagonists & inhibitors,  metabolism
MAP Kinase Kinase 2 / antagonists & inhibitors,  metabolism
Morpholines / pharmacology
Nitriles / pharmacology
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism
Protein Kinase Inhibitors / pharmacology
Rats, Sprague-Dawley
Receptor, erbB-2 / antagonists & inhibitors,  metabolism*
Sodium / metabolism*
Sodium Channel Blockers / pharmacology
Transforming Growth Factor alpha / metabolism
Tyrphostins / pharmacology
Grant Support
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Benzothiazoles; 0/Butadienes; 0/Chromones; 0/Epithelial Sodium Channels; 0/Erbb2 protein, rat; 0/Flavonoids; 0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/Morpholines; 0/Nitriles; 0/Protein Kinase Inhibitors; 0/Sodium Channel Blockers; 0/Transforming Growth Factor alpha; 0/Tyrphostins; 0/U 0126; 0/tyrphostin AG825; 117147-70-3/amphiregulin; 149176-25-0/heparin-binding EGF-like growth factor; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 2609-46-3/Amiloride; 62229-50-9/Epidermal Growth Factor; 7440-23-5/Sodium; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC protein, mouse; EC, erbB-2; EC Kinase Kinase 1; EC Kinase Kinase 2

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