Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expression.
Low 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.
Gaultier
Alban
A
Department of Pathology, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Salicioni
Ana Maria
AM
Arandjelovic
Sanja
S
Gonias
Steven L
SL
D000818:Animals; D001710:Biotin / Q000737:chemistry; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism / Q000502:physiology*; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013499:Surface Properties; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D017077:Culture Media, Conditioned; D026502:LDL-Receptor Related Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D012333:RNA, Messenger; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D001710:Biotin; D005340:Fibrinogen; D003094:Collagen