on May 27, 2004
Published online before print May 27, 2004, doi: 10.1161/01.ATV.0000133607.80554.09
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 16, 2003
Accepted on April 30, 2004
LRP1B Attenuates the Migration of Smooth Muscle Cells by Reducing Membrane Localization of Urokinase and PDGF Receptors
Kousei Tanaga ;
From the Departments of Clinical Cell Biology (K. Tanaga, Y.Z., T.K., S.H., K. Takahashi, Y.S.) and Genome Research and Clinical Application (H.B.), Chiba University Graduate School of Medicine, Chiba, Japan; Omigawa Hospital (M.I., K.M.), Omigawa, Japan; and the Department of Molecular Genetics (S.H., W.J.S.), Biocenter and University of Vienna, Vienna, Austria.
* To whom correspondence should be addressed. E-mail: hbujo{at}faculty.chiba-u.jp.
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) 
.
Methods and 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 PDGFR 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.
Key words: smooth muscle cells • LRP1B • PDGF receptor • uPA receptor • migration
This article has been cited by other articles:
 |
|
 |
|
  K. Ohwaki, H. Bujo, M. Jiang, H. Yamazaki, W. J. Schneider, and Y. Saito A Secreted Soluble Form of LR11, Specifically Expressed in Intimal Smooth Muscle Cells, Accelerates Formation of Lipid-Laden Macrophages Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1050 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-X. Liu, S. Ranganathan, S. Robinson, and D. K. Strickland {gamma}-Secretase-mediated Release of the Low Density Lipoprotein Receptor-related Protein 1B Intracellular Domain Suppresses Anchorage-independent Growth of Neuroglioma Cells J. Biol. Chem., March 9, 2007; 282(10): 7504 - 7511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Bujo and Y. Saito Modulation of Smooth Muscle Cell Migration by Members of the Low-Density Lipoprotein Receptor Family Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1246 - 1252. [Abstract] [Full Text] [PDF]
|
|