Enhanced expression of the LDL receptor family member LR11 increases migration of smooth muscle cells in vitro.
BACKGROUND
LR11, a member of the LDL receptor family, is highly expressed in vascular smooth muscle cells (SMCs) of the hyperplastic intima but not media. To further clarify the involvement of LR11 in the process of atherosclerosis, we have characterized the migration and invasion activities of LR11-overexpressing SMCs.


RESULTS
LR11 cDNA was transfected into the rat SMC line A7r5. Compared with mock cells (C-1), in the presence of platelet-derived growth factor-BB, the transfected cells (R-1 and R-2) showed 3.5- to 4.0-fold higher expression of LR11 protein, 1.7- to 1.8-fold increased migration, and 2.0- to 2.2-fold elevated invasion activities, respectively. The increases were essentially abolished by the addition of receptor-associated protein, anti-LR11 antibodies, or apolipoprotein E. Immunological analyses showed that urokinase-type plasminogen activator receptor (uPAR) levels were increased in LR11-overexpressing cells. Anti-urokinase-type plasminogen activator (uPA) and anti-uPAR antibodies reduced the migration and invasion activities of R-1 and R-2 cells to baseline levels. Receptor-associated protein, anti-LR11 antibodies, and apolipoprotein E decreased uPAR expression in the LR11-overexpressing cells by approximately 50%. Cellular catabolism of uPAR was significantly decreased in R-1 and R-2 cells compared with control. Cultured SMCs isolated from intima of atherosclerotic rabbit aortas showed increased expression levels of LR11 and uPAR and enhanced migration and invasion compared with SMCs from medial layers.


CONCLUSIONS
Overexpression of LR11 induces enhanced migration and invasion activities of intimal SMCs in vitro, probably through its regulation of the uPA/uPAR system.
Zhu
Yanjuan
Y
Department of Clinical Cell Biology (F5), Chiba University Graduate School of Medicine, Chiba, Japan.
Bujo
Hideaki
H
Yamazaki
Hiroyuki
H
Hirayama
Satoshi
S
Kanaki
Tatsuro
T
Takahashi
Kazuo
K
Shibasaki
Manabu
M
Schneider
Wolfgang J
WJ
Saito
Yasushi
Y
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001057:Apolipoproteins E / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D007700:Kinetics; D026563:LDL-Receptor Related Protein-Associated Protein / Q000494:pharmacology; D026901:Membrane Transport Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000906:Antibodies; D001057:Apolipoproteins E; D026563:LDL-Receptor Related Protein-Associated Protein; D026901:Membrane Transport Proteins; C524900:Plaur protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D055293:Receptors, Urokinase Plasminogen Activator; C491167:Sorl1 protein, rat; D014568:Urokinase-Type Plasminogen Activator