Integrin regulation of vascular smooth muscle cell migration

整合素对血管平滑肌细胞迁移的调节

• 批准号: 11838014
• 负责人: KOYAMA Hidenori
• 金额: $ 2.05万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11838014/
• 关键词: atherosclerosis; plasminogen activator inhibitor-1(PAI-1); plasminogen activator (uPA); uPA receptor (uPAR); PDGF; alpha v beta 3 integrin; collagen type I; プラスミノーゲン・アフチベーター・インヒビター(PAI-1); プラスミノーゲン・アフチベーター(uPA); αvβ_3インテグリン; プラスミノーゲン・アクチベーター・インヒ

Smooth muscle cell (SMC) migration from the medial layer of vessels into forming lesions contributes to atherogenesis. In this study, we demonstrate that SMC culture on polymerized collagen, in contrast with culture on monomer collagen, significantly inhibits αvβ3-dependent SMC migration on vitronectin or osteopontin, but does not alter migration on type I collagen or fibronectin. After culture on polymerized collagen, αvβ3 integrin clustering in focal adhesions on vitronectin is suppressed without a significant change in extracellular expression of αvβ3. Following culture on monomer collagen and plating on vitronectin, plasminogen activator inhibitor-1 (PAI-1) co-localizes with αvβ3 and a blocking PAI-1 antibody inhibits SMC migration. In contrast, polymerized collagen culture suppresses PAI-1 secretion and its accumulation at focal adhesions, while urinary plasminogen activator (uPA) secretion and uPA receptor (uPAR) expression are stimulated. Suppression of SMC migration on vitronectin by polymerized collagen is restored by addition of exogenous PAI-1 protein but not by latent inactive PAI-1, and the effects of PAI-1 are blocked by co-treatment of the SMC with uPA.Finally active PAI-1, but not latent inactive PAI-1, colocalizes with αvβ3 integrin, and blocking antibody for αvβ3 inhibits SMC adhesion to PAI-1. Thus, polymerized collagen appears to dynamically regulate SMC migratory response through modulation of αvβ3 integrin function and the uPA-uPAR-PAI-1 system.

平滑肌细胞（SMC）从血管中层迁移到形成的病变有助于动脉粥样硬化的形成。在这项研究中，我们证明，SMC在聚合胶原上培养，与在单体胶原上培养相比，显著抑制αvβ3依赖性SMC在玻连蛋白或骨桥蛋白上的迁移，但不改变在I型胶原或纤连蛋白上的迁移。在聚合胶原上培养后，在玻连蛋白上的粘着斑中聚集的αvβ3整联蛋白被抑制，而αvβ3的细胞外表达没有显著变化。在单体胶原上培养并在玻连蛋白上铺板后，纤溶酶原激活物抑制剂-1（派-1）与αvβ3共定位，阻断派-1抗体抑制SMC迁移。相比之下，聚合胶原培养抑制派-1分泌及其在局灶性粘连处的积聚，而刺激尿纤溶酶原激活物（uPA）分泌和uPA受体（uPAR）表达。加入外源性派-1蛋白可恢复聚合胶原对SMC在玻连蛋白上迁移的抑制作用，而不受潜在失活派-1的影响，同时加入uPA可阻断派-1的作用，最后活性派-1可与αvβ3整合素共定位，而非潜在失活派-1，αvβ3阻断抗体可抑制SMC与派-1的粘附。因此，聚合胶原似乎通过调节αvβ3整合素功能和uPA-uPAR-派-1系统动态调节SMC迁移反应。

项目成果

Tanaka S et al: "Suppression of integrin αvβ_3-dependent smooth muscle cell migration by fibrillar collagen"Circulation. 100(18). 1-694 (1999)

Tanaka S 等人：“纤维状胶原对整合素αvβ_3依赖性平滑肌细胞迁移的抑制”循环100(18)。

Tanaka S, Koyama H et al: "Suppression of inbegrin αvβ_3-dependent smooth muscle cell migration by fibrillar type I collagen : Involvement of plasminogen activator inhibitor-1"Circulation. 100(18). I-694 (1999)

Tanaka S、Koyama H 等人：“纤维状 I 型胶原对 inbegrin αvβ_3 依赖性平滑肌细胞迁移的抑制：纤溶酶原激活剂抑制剂-1 的参与”循环 100(18)。

Ichii T: "Fibrillar collagen specifically regulates human vascular smooth muscle cell genes involved in cellular responses and the pericellular matrix environment"Circulation Research. 88. 460-467 (2001)

Ichii T：“纤维状胶原蛋白特异性调节参与细胞反应和细胞周基质环境的人类血管平滑肌细胞基因”循环研究。

Tanaka S: "Suppression of integrin alpha v beta 3-dependent smooth muscle cell migration by fibrillar collagen"Circulation. 100. I-694 (1999)

Tanaka S：“纤维状胶原蛋白抑制整合素 α v β 3 依赖性平滑肌细胞迁移”循环。

Tanaka S: "Suppression of integrin αvβ3-dependent smooth muscle cell migration by fibrillar collagen"Circulation. 100. I694 (1999)

Tanaka S：“纤维状胶原对整合素 αvβ3 依赖性平滑肌细胞迁移的抑制”100。I694 (1999)。