title: LRP1B attenuates the migration of smooth muscle cells by reducing membrane localization of urokinase and PDGF receptors.
abstract: OBJECTIVE
  Studies on the involvement of low-density lipoprotein receptor relatives (LRs) in atherosclerosis have recently gained new focus because of the specific expression of certain of these receptors in the thickened intima. Here, we show that LRP1B, a member of LRs, modulates the migration of smooth muscle cells (SMCs) by increasing the degradation of membrane receptors, urokinase-type plasminogen activator receptor (uPAR), and platelet-derived growth factor receptor (PDGFR) beta.
  
  
  RESULTS
  Immunohistochemistry showed that LRP1B expression in human coronary arteries is localized to the intimal SMCs near the plaque surface as well as to medial SMCs. LRP1B expression levels in cultured SMCs increase at the late phase of proliferation. Cell surface and internalization assays, in combination with coimmunoprecipitation experiments, showed that LRP1B binds and internalizes uPAR. Metabolic labeling analysis demonstrated that anti-LRP1B IgY decreased the catabolism of uPAR. In addition, the anti-LRP1B antibody raised PDGFRbeta protein and PDGFR-mediated phosphorylation levels of ERK1/2. Finally, the anti-LRP1B IgY enhanced the migration and invasion of SMCs in the presence of PDGF-BB.
  
  
  CONCLUSIONS
  LRP1B modulates the catabolism of uPAR and PDGFR, affecting the migration of SMCs. This functional characterization of LRP1B opens novel avenues for elucidating the (patho)physiological significance of SMC migration in atheromatous plaques.
authors.affiliation: Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Kousei
authors.initials: K
authors.lastname: Tanaga
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kanaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Keiji
authors.initials: K
authors.lastname: Mikami
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Schneider
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000789:Angina, Unstable / Q000473:pathology; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D002645:Chickens; D003331:Coronary Vessels / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D017539:Tunica Intima / Q000473:pathology
chemical_list: C016512:IgY; D007136:Immunoglobulins; C434476:LRP1B protein, human; C524898:PLAUR protein, human; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3