Source:http://linkedlifedata.com/resource/pubmed/id/15522985
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-2-4
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pubmed:abstractText |
Amiloride-sensitive sodium entry, via the epithelial sodium channel (ENaC), is the rate-limiting step for Na+ absorption in kidney collecting ducts, and epidermal growth factor (EGF) inhibits Na+ transport and ENaC expression. A pathognomonic feature of polycystic kidney disease (PKD) is EGF receptor mislocalization to the apical plasma membrane and EGF/EGF receptor axis overactivity. Immunohistochemical and biochemical analysis revealed mislocalization of EGF receptor and excessive activation of the p42/44 extracellular signal-regulated protein kinase pathway (ERK1/2) in kidneys from cystic mice compared with noncystic littermates. Primary monolayer cultures of noncystic and cystic murine collecting duct principal cells were used to identify aberrant EGF-dependent ERK1/2 activation and regulation of Na+ transport associated with autosomal recessive PKD. Addition of EGF to the basolateral bathing solution of noncystic or cystic monolayers led to p42/44 phosphorylation and inhibition of Na+ transport (30-35%), whereas apical EGF was effective only in monolayers derived from cystic mice. p42/44 Phosphorylation and inhibition of Na+ transport were prevented by prior treatment of the cells with an ERK kinase inhibitor. Chronic treatment (24 h) of noncystic and cystic monolayers with basolateral EGF elicited sustained inhibition of Na+ absorption (50-55%) and a reduction in steady-state ENaC mRNA levels (50-75%). In contrast, addition of EGF to the apical bathing solution (24 h) had no effect in noncystic monolayers but led to inhibition of Na+ transport (50-60%) and decreased ENaC expression (45-60%) in cystic cells. Pretreatment of the monolayers with an ERK kinase inhibitor abolished the chronic effects of EGF on Na+ transport. The results of these studies reveal that the mislocalized apical EGF receptors are functionally coupled to the ERK pathway and that abnormal EGF-dependent regulation of ENaC function and expression may contribute to PKD pathophysiology.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amiloride,
http://linkedlifedata.com/resource/pubmed/chemical/Diuretics,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Epithelial Sodium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1931-857X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
288
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
F474-82
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:15522985-Amiloride,
pubmed-meshheading:15522985-Animals,
pubmed-meshheading:15522985-Blotting, Western,
pubmed-meshheading:15522985-Cell Line,
pubmed-meshheading:15522985-Cell Proliferation,
pubmed-meshheading:15522985-Cell Separation,
pubmed-meshheading:15522985-Diuretics,
pubmed-meshheading:15522985-Electrophysiology,
pubmed-meshheading:15522985-Enzyme Activation,
pubmed-meshheading:15522985-Epidermal Growth Factor,
pubmed-meshheading:15522985-Epithelial Sodium Channel,
pubmed-meshheading:15522985-Immunohistochemistry,
pubmed-meshheading:15522985-Immunoprecipitation,
pubmed-meshheading:15522985-Kidney Tubules, Collecting,
pubmed-meshheading:15522985-Mice,
pubmed-meshheading:15522985-Microscopy, Confocal,
pubmed-meshheading:15522985-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15522985-Phosphorylation,
pubmed-meshheading:15522985-Polycystic Kidney, Autosomal Recessive,
pubmed-meshheading:15522985-RNA, Messenger,
pubmed-meshheading:15522985-Receptor, Epidermal Growth Factor,
pubmed-meshheading:15522985-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15522985-Sodium,
pubmed-meshheading:15522985-Sodium Channels
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pubmed:year |
2005
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pubmed:articleTitle |
Abnormal EGF-dependent regulation of sodium absorption in ARPKD collecting duct cells.
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pubmed:affiliation |
Department of Pediatrics and Physiology and Biophysics, Rainbow Center for Childhood Polycystic Kidney Disease, Case Western Reserve University, Cleveland, OH 44106-4948, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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