Source:http://linkedlifedata.com/resource/pubmed/id/15284295
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2004-8-2
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| pubmed:abstractText |
The urokinase receptor (uPAR) attenuates myofibroblast recruitment and fibrosis in the kidney. This study examined the role of uPAR and its co-receptor LDL receptor-related protein (LRP) in the regulation of kidney fibroblast proliferation and extracellular signal-regulated kinase (ERK) signaling. Compared with uPAR+/+ cells, uPAR-/- kidney fibroblasts were hyperproliferative. UPAR-/- fibroblast proliferation was 60% inhibited by an ERK kinase inhibitor. LRP protein was reduced and extracellular accumulation of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) proteins were greater in uPAR-/- cultures. Addition of functional uPA protein or LRP antisense RNA significantly increased ERK signaling and cell mitosis in both genotypes. Enhanced uPAR-/- fibroblast proliferation was reversed by a recombinant nonfunctional uPA peptide. The density of cell-bound fluor-uPA was similar between uPAR-/- and uPAR+/+ fibroblasts (78 +/- 6 versus 92 +/- 16 units). These data suggest that uPAR-deficient kidney fibroblasts express lower levels of its scavenger co-receptor LRP, resulting in greater extracellular accumulation of uPA and PAI-1. Enhanced proliferation of uPAR-/- fibroblasts seems to be mediated by uPA-dependent ERK signaling via an alternative urokinase receptor.
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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/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Plaur protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Urokinase Plasminogen...,
http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1046-6673
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
15
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2090-102
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:15284295-Animals,
pubmed-meshheading:15284295-Cell Division,
pubmed-meshheading:15284295-Cells, Cultured,
pubmed-meshheading:15284295-Fibroblasts,
pubmed-meshheading:15284295-Kidney,
pubmed-meshheading:15284295-Low Density Lipoprotein Receptor-Related Protein-1,
pubmed-meshheading:15284295-MAP Kinase Signaling System,
pubmed-meshheading:15284295-Mice,
pubmed-meshheading:15284295-Mice, Inbred C57BL,
pubmed-meshheading:15284295-Mice, Mutant Strains,
pubmed-meshheading:15284295-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15284295-Phenotype,
pubmed-meshheading:15284295-Phosphorylation,
pubmed-meshheading:15284295-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:15284295-Receptors, Cell Surface,
pubmed-meshheading:15284295-Receptors, Urokinase Plasminogen Activator,
pubmed-meshheading:15284295-Ureteral Obstruction,
pubmed-meshheading:15284295-Urokinase-Type Plasminogen Activator
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| pubmed:year |
2004
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| pubmed:articleTitle |
Mitogenic signaling of urokinase receptor-deficient kidney fibroblasts: actions of an alternative urokinase receptor and LDL receptor-related protein.
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| pubmed:affiliation |
University of Washington, Children's Hospital and Regional Medical Center, Division of Nephrology, Seattle, WA 98105, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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