Molecular analysis and clinical application of LR11 in SMCs.

SMCs中LR11的分子分析及临床应用。

• 批准号: 17590917
• 负责人: BUJO Hideaki
• 金额: $ 2.24万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590917/
• 关键词: Arteriosclerosis; Smooth muscle cell; Blood vessel; Migration; Differentiation

The aim of study is to clarify the molecular mechanism of LR11, a gene specifically expressed in intimal SMCs, in the development of atherosclerosis.1. Establishment and characterization of LR11 knockout mice.The exon 1 of LR11 gene was replaced by NEO gene. The birth and growth properties of LR11-/- mice did not show any obvious difference from those of LR11+/+ mice. The intimal thickness after cuff injury in LR11-/- mice was significantly reduced compared with that in LR11+/+ mice. The cultured LR11-/- SMCs showed a significant decrease in migration activity under PDGF-BB stimulation compared with the LR11+/+ SMCs,2. The functional analyses of secreted soluble form of LR11A secreted soluble form of LR11 was established by the deletion of membrane-spanning and intracellular regions. The soluble form showed the inducing activity for migration, attachment and lipd incorporation of cultured macrophages, in addition to the migration activity of SMCs.3. Regulation of LR11 gene in SMCs.The LR11 gene transcription was significantly increased by PDGF-BB, and the increased transcription was inhibited by the treatment of pitavastatin. The LR11-overexpressing SMCs showed the decreased response to pitavastatin for migration activity.These results show that the aim of study could be almost completed in the study years.

研究的目的是阐明在内膜SMC中特异性基因的LR11的分子机制，在动脉粥样硬化的发展中。1。 LR11敲除小鼠的建立和表征。LR11基因的外显子1被NEO基因取代。 LR11 - / - 小鼠的出生和生长特性与LR11+/+小鼠的分歧没有任何明显的差异。与LR11+/+小鼠相比，LR11-/ - 小鼠袖带损伤后的内膜厚度显着降低。与LR11+/+ SMC相比，培养的LR11 - / - SMC在PDGF-BB刺激下显示出迁移活性的显着降低。 LR11a分泌的LR11的分泌可溶性形式的功能分析是通过缺失膜跨​​膜和细胞内区域的。除SMC的迁移活性外，可溶性形式显示了培养巨噬细胞的迁移，附着和LIPD掺入的诱导活性。3。 PDGF-BB在SMC中调节LR11基因的LR11基因转录显着增加，并且通过治疗pitavastatin抑制了转录的增加。过表达LR11的SMC显示了对pitavastatin对迁移活性的反应下降。这些结果表明，在研究年份，研究的目的几乎可以完成。

项目成果

A potent activator of PPARalpha and gamma reduces the vascular cell recruitment and inhibits the intimal thickning in hypercholesterolemic rabbits.

PPARα 和 γ 的有效激活剂可减少高胆固醇血症兔的血管细胞募集并抑制内膜增厚。

• 发表时间: 2005
• 期刊: Atherosclerosis. 178(1)
• 作者: Seki N;Bujo H;Jiang M;Shibasaki M;Takahashi K;Hashimoto N;Saito Y.
• 通讯作者: Saito Y.

Modulation of smooth muscle cell migration by members of the low-density lipoprotein receptor family.

• DOI: 10.1161/01.atv.0000219692.78477.17
• 发表时间: 2006-06
• 期刊: Arteriosclerosis, thrombosis, and vascular biology
• 作者: H. Bujo;Y. Saito

A Selected Soluble Form of LR11, Specifically Expressed in Intimal Smooth Muscle Cells Accelerates Formation of Lipid - Laden Macrophages.

精选的 LR11 可溶形式，在内膜平滑肌细胞中特异性表达，可加速富含脂质的巨噬细胞的形成。

• 发表时间: 2007
• 期刊: Arterioscler Thromb Vasc Biol. Published on line
• 作者: Ohwaki K;Bujo H;Yamazaki H;Schneider WJ;Saito Y.
• 通讯作者: Saito Y.

A Secreted Soluble Form of LR11, Speciffically Expressed in Intimal Smooth Muscle Cells, Acclerates Formation of Lipid-Laden Macrophages.

LR11 是一种分泌型可溶形式，在内膜平滑肌细胞中特异性表达，可加速富含脂质的巨噬细胞的形成。

• 发表时间: 2007
• 期刊: Arterioscler Thromb Vasc Biol. Mar 1 (Epub ahead of print)
• 作者: Ohwaki K;Bujo H;Jiang M;Yamazaki H;Schneider WJ;Saito Y.
• 通讯作者: Saito Y.

Pitavastatin attnuate the PDGF-induced LR11/u PA receptor mediate migragion of smooth muscle cells.

Pitavastatin 减弱 PDGF 诱导的 LR11/u PA 受体介导的平滑肌细胞迁移。

• 发表时间: 2006
• 期刊: Biochem Biophys Res Commun 348(4)
• 作者: Jiang M;Bujo H;Zhu Y;Yamasaki H;Hirayama S;Kanakki T;Shibasaki M;Takahashi K;Schneid or WJ;Saito Y.
• 通讯作者: Saito Y.