Source:http://linkedlifedata.com/resource/pubmed/id/16870608
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
39
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pubmed:dateCreated |
2006-9-25
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pubmed:abstractText |
Renal cyst formation is the hallmark of autosomal dominant polycystic kidney disease (ADPKD). ADPKD cyst-lining cells have an increased proliferation rate and are surrounded by an abnormal extracellular matrix (ECM). We have previously shown that Laminin 5 (Ln-5, a alpha(3)beta(3)gamma(2) trimer) is aberrantly expressed in the pericystic ECM of ADPKD kidneys. We report that ADPKD cells in primary cultures produce and secrete Ln-5 that is incorporated to the pericystic ECM in an in vitro model of cystogenesis. In monolayers, purified Ln-5 induces ERK activation and proliferation of ADPKD cells, whereas upon epidermal growth factor stimulation blocking endogenously produced Ln-5 with anti-gamma(2) chain antibody reduces the sustained ERK activation and inhibits proliferation. In three-dimensional gel culture, addition of purified Ln-5 stimulates cell proliferation and cyst formation, whereas blocking endogenous Ln-5 strongly inhibits cyst formation. Ligation of alpha(6)beta(4) integrin, a major Ln-5 receptor aberrantly expressed by ADPKD cells, induces beta(4) integrin phosphorylation, ERK activation, cell proliferation, and cyst formation. These findings indicate that Ln-5 is an important regulator of ADPKD cell proliferation and cystogenesis and suggest that Ln-5 gamma(2) chain and Ln-5-alpha(6)beta(4) integrin interaction both contribute to these phenotypic changes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha6beta4,
http://linkedlifedata.com/resource/pubmed/chemical/Laminin,
http://linkedlifedata.com/resource/pubmed/chemical/laminin alpha 3
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29181-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16870608-Cell Line,
pubmed-meshheading:16870608-Cell Proliferation,
pubmed-meshheading:16870608-Dimerization,
pubmed-meshheading:16870608-Epidermal Growth Factor,
pubmed-meshheading:16870608-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:16870608-Gene Expression Regulation,
pubmed-meshheading:16870608-Humans,
pubmed-meshheading:16870608-Integrin alpha6beta4,
pubmed-meshheading:16870608-Kidney Diseases, Cystic,
pubmed-meshheading:16870608-Laminin,
pubmed-meshheading:16870608-Microscopy, Phase-Contrast,
pubmed-meshheading:16870608-Phosphorylation,
pubmed-meshheading:16870608-Polycystic Kidney Diseases,
pubmed-meshheading:16870608-Protein Binding
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pubmed:year |
2006
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pubmed:articleTitle |
Laminin 5 regulates polycystic kidney cell proliferation and cyst formation.
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pubmed:affiliation |
Université Paris-Descartes, FacultédeMédecine, Inserm U813, AP-HP, Hôpital Necker-Enfants-Malades, Service Néphrologie, 149 Rue de Sévres, 75015 Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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