Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expression.

TitleRegulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expression.
Publication TypeJournal Article
Year of Publication2006
AuthorsGaultier A, Salicioni AM, Arandjelovic S, Gonias SL
JournalThe Journal of biological chemistry
Volume281
Issue11
Pagination7332-40
Date Published2006 Mar 17
ISSN0021-9258
KeywordsAnimals, Biotin, Cell Line, Cell Membrane, Cloning, Molecular, Collagen, Culture Media, Conditioned, Electrophoresis, Gel, Two-Dimensional, Electrophoresis, Polyacrylamide Gel, Endocytosis, Extracellular Matrix, Fibrinogen, Gene Expression Regulation, Humans, LDL-Receptor Related Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Mass Spectrometry, Mice, Microscopy, Fluorescence, Neovascularization, Pathologic, Phosphorylation, Proteomics, Receptors, LDL, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Signal Transduction, Surface Properties, Tumor Suppressor Proteins
AbstractLow density lipoprotein receptor-related protein-1 (LRP-1) is a catabolic receptor for extracellular matrix (ECM) structural proteins and for proteins that bind to ECM. LRP-1 also is implicated in integrin maturation. In this study, we applied a proteomics strategy to identify novel proteins involved in ECM modeling that are regulated by LRP-1. We show that LRP-1 deficiency in murine embryonic fibroblasts (MEFs) is associated with increased levels of type III collagen and pigment epithelium-derived factor, which accumulate in the substratum surrounding cells. The collagen receptor, uPAR-AP/Endo-180, is also increased in LRP-1-deficient MEFs. Human LRP-1 reversed the changes in protein expression associated with LRP-1 deficiency; however, the endocytic activity of LRP-1 was not involved. Instead, regulation occurred at the mRNA level. Inhibition of c-Jun amino-terminal kinase (JNK) blocked type III collagen expression in LRP-1-deficient MEFs, suggesting regulation of JNK activity as a mechanism by which LRP-1 controls mRNA expression. The ability of LRP-1 to regulate expression of the factors identified here suggests a role for LRP-1 in determining blood vessel structure and in angiogenesis.
DOI10.1074/jbc.M511857200
Alternate JournalJ. Biol. Chem.
PubMed ID16407289