|EGF and its related growth factors mediate sodium transport in mpkCCDc14 cells via ErbB2 (neu/HER-2) receptor.|
|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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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|Title: Journal of cellular physiology Volume: 223 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Apr|
|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|
|Languages: eng Pagination: 252-9 Citation Subset: IM|
|J. Cell. Physiol. 223: 252-259, 2010. (c) 2009 Wiley-Liss, Inc.|
|Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Benzothiazoles / pharmacology
Butadienes / pharmacology
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
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
Receptor, erbB-2 / antagonists & inhibitors, metabolism*
Sodium / metabolism*
Sodium Channel Blockers / pharmacology
Transforming Growth Factor alpha / metabolism
Tyrphostins / pharmacology
|DK62345/DK/NIDDK NIH HHS|
|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 126.96.36.199/Erbb2 protein, mouse; EC 188.8.131.52/Receptor, erbB-2; EC 184.108.40.206/MAP Kinase Kinase 1; EC 220.127.116.11/MAP Kinase Kinase 2|
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