Functional analysis of LR11 in vascular smooth muscle cells

LR11在血管平滑肌细胞中的功能分析

• 批准号: 12835002
• 负责人: BUJO Hideaki
• 金额: $ 2.37万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12835002/
• 关键词: LDLR; LR11; Atherosclerosis; Smooth muscle cells; 動脈硬化; LDL受容体; 血管

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. LR11 cDNA was transfected into the rat SMC line, A7r5. Compared to mock cells (C-1), in the presence of PDGF-BB the transfected cells (R-1 and R-2) showed 3.5-4.0-fold higher expression of LR11 protein, 1.7-1.8-fold increased migration, and 2.0-2.2-fold elevated invasion activities, respectively. The increases were essentially abolished by the addition of receptor-associated protein (RAP), anti-LR11 antibodies, or Apo E. Immunological analyzes showed that urokinase-type plasminogen activator receptor (uPAR) levels were increased in LR11-overexpressing cells. Anti-uPA and anti-uPAR antibodies reduced the migration and invasion activities of R-1 and R-2 cells to baseline levels. RAP, anti-ER11 antibodies, and apo E decreased uPAR expression in the LR11-overexpressing cells by 〜50%. Cellular catabolism of uPAR was significantly decreased in R-1 and R-2 cells compared to control. Cultured SMCs isolated from intimae of atherosclerotic rabbit aortas showed increased expression levels of LR11 and uPAR, and enhanced migration and invasion compared to SMCs from medial layers. Overexpression of LR11 induces enhanced migration and invasion activities of intimal SMCs in vitro, likely via its regulation of the uPA/uPAR system.

LR11，在血管平滑肌细胞（SMC）中表达的LDL受体的成员。 ，A7R5与模拟细胞（C-1）B相比，转染的细胞（R-1和R-2）显示了LR11蛋白的3.5-4.0倍，迁移增加了1.7-1.8倍，2.0-2.2倍通过添加与受体相关的蛋白质（RAP），抗LR11抗体或ApoE。免疫学分析可以消除升高活性抗抗体将R-1和R-1和R-1 2细胞的迁移和侵入活性降低到基线水平。与对照组相比，R-1和R-2细胞的OFAR显着降低。系统。

项目成果

Miyazaki O, Kobayashi J, Fukamachi I, Miida T, Bujo H, Saito Y.: "A new sandwich enzyme immunoassay for measurement of plasma pre-betal-HDL level"J Lipid Res.. 41(12). 2083-2088 (2000)

Miyazaki O、Kobayashi J、Fukamachi I、Miida T、Bujo H、Saito Y.：“一种用于测量血浆前 β-HDL 水平的新型夹心酶免疫测定法”J Lipid Res.. 41(12)。

Kanaki T, Morisaki N, Bujo H, Takahashi K, Ishii I, Saito Y: "The regulatory expression of procollagen COOH-terminal proteinase enhancer in the proliferation of vascular smooth muscle cells."Biochem Biophys Res Commun. 270(3). 1049-54 (2000)

Kanaki T、Morisaki N、Bujo H、Takahashi K、Ishii I、Saito Y：“前胶原 COOH 末端蛋白酶增强剂在血管平滑肌细胞增殖中的调节表达。”Biochem Biophys Res Commun。

Zhu Y., et al.: "Enhanced expression of LDLR family member LR11 increases migration of smooth muscle cells in vitro"Circulation. In press. (2002)

Zhu Y.等人：“LDLR家族成员LR11的表达增强可增加平滑肌细胞的体外迁移”循环。

Hirayama S, Bujo H, Yamazaki H, Kanaki T, Takahashi K, Saito Y.: "Differential expression of LR11 during proliferation and differentiation of cultured ~neuroblastoma cells"Biochem Biophys Res Commun. 275(2). 365-562 (2000)

Hirayama S、Bujo H、Yamazaki H、Kanaki T、Takahashi K、Saito Y.：“培养的神经母细胞瘤细胞增殖和分化过程中 LR11 的差异表达”Biochem Biophys Res Commun。

Ishii I, et al.: "Histological and functional analysis of vascular smooth muscle cells in a novel culture system with honeycomb-like structure Atherosclerosis"Atherosclerosis. 155. 377-384 (2001)

Ishii I 等人：“具有蜂窝状结构的新型培养系统中血管平滑肌细胞的组织学和功能分析”动脉粥样硬化。