Linked Life Data

20345844

Source:http://linkedlifedata.com/resource/pubmed/id/20345844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-5-6
pubmed:abstractText
Our previous studies have demonstrated increased expression of insulin-like growth factor binding protein-5 (IGFBP-5) in fibrotic tissues and IGFBP-5 induction of extracellular matrix (ECM) components. The mechanism resulting in increased IGFBP-5 in the extracellular milieu of fibrotic fibroblasts is unknown. Since Caveolin-1 (Cav-1) has been implicated to play a role in membrane trafficking and signal transduction in tissue fibrosis, we examined the effect of Cav-1 on IGFBP-5 internalization, trafficking and secretion. We demonstrated that IGFBP-5 localized to lipid rafts in human lung fibroblasts and bound Cav-1. Cav-1 was detected in the nucleus in IGFBP-5-expressing fibroblasts, within aggregates enriched with IGFBP-5, suggesting a coordinate trafficking of IGFBP-5 and Cav-1 from the plasma membrane to the nucleus. This trafficking was dependent on Cav-1 as fibroblasts from Cav-1 null mice had increased extracellular IGFBP-5, and as fibroblasts in which Cav-1 was silenced or lipid raft structure was disrupted through cholesterol depletion also had defective IGFBP-5 internalization. Restoration of Cav-1 function through administration of Cav-1 scaffolding peptide dramatically increased IGFBP-5 uptake. Finally, we demonstrated that IGFBP-5 in the ECM protects fibronectin from proteolytic degradation. Taken together, our findings identify a novel role for Cav-1 in the internalization and nuclear trafficking of IGFBP-5. Decreased Cav-1 expression in fibrotic diseases likely leads to increased deposition of IGFBP-5 in the ECM with subsequent reduction in ECM degradation, thus identifying a mechanism by which reduced Cav-1 and increased IGFBP-5 concomitantly contribute to the perpetuation of fibrosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1582-4934
pubmed:author
pubmed:copyrightInfo
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
957-69
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:20345844-Animals, pubmed-meshheading:20345844-Caveolin 1, pubmed-meshheading:20345844-Cell Compartmentation, pubmed-meshheading:20345844-Cell Extracts, pubmed-meshheading:20345844-Cell Nucleus, pubmed-meshheading:20345844-Cytoplasm, pubmed-meshheading:20345844-Endocytosis, pubmed-meshheading:20345844-Extracellular Matrix, pubmed-meshheading:20345844-Extracellular Space, pubmed-meshheading:20345844-Fibroblasts, pubmed-meshheading:20345844-Fibrosis, pubmed-meshheading:20345844-Humans, pubmed-meshheading:20345844-Insulin-Like Growth Factor Binding Protein 3, pubmed-meshheading:20345844-Insulin-Like Growth Factor Binding Protein 5, pubmed-meshheading:20345844-Intracellular Space, pubmed-meshheading:20345844-Mice, pubmed-meshheading:20345844-Mice, Inbred C57BL, pubmed-meshheading:20345844-Protein Binding, pubmed-meshheading:20345844-Protein Transport, pubmed-meshheading:20345844-Subcellular Fractions
pubmed:year
2011
pubmed:articleTitle
Decreased caveolin-1 levels contribute to fibrosis and deposition of extracellular IGFBP-5.
pubmed:affiliation
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural