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整合素在大隐静脉血管平滑肌细胞迁移中的作用。

The role of integrins in saphenous vein vascular smooth muscle cell migration.

作者信息

Itoh H, Nelson P R, Mureebe L, Horowitz A, Kent K C

机构信息

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

出版信息

J Vasc Surg. 1997 Jun;25(6):1061-9. doi: 10.1016/s0741-5214(97)70130-7.

Abstract

PURPOSE

Smooth muscle cell (SMC) migration is an essential feature of the intimal hyperplastic process that so frequently limits the patency of vascular reconstructions. The purpose of this investigation was to evaluate the effect of a series of integrins, or cell surface receptors that mediate cellular attachment, on platelet-derived growth factor (PDGF) and extracellular matrix (ECM) protein-induced migration of human SMCs.

METHODS

Immunofluorescence staining was used to search for various integrins and subunits on the surface of SMCs derived from human saphenous vein. Chemotaxis and haptotaxis of SMCs to various matrix proteins and PDGF were assayed using a 48-well microchemotaxis chamber in the presence or absence of antibodies that blocked the function of these integrins.

RESULTS

Several subunits (beta 1, alpha 2, alpha 5) and one integrin (alpha v beta 3) were identified in saphenous vein SMCs. The beta 1 integrin antibody inhibited chemotaxis to collagen I and IV, laminin, and PDGF. The alpha 2 integrin antibody inhibited collagen I and IV, and laminin-induced chemotaxis. The alpha 5 integrin antibody had no effect on SMC migration. The alpha v beta 3 integrin antibody inhibited chemotaxis to PDGF but not to the ECM proteins.

CONCLUSIONS

Integrins are necessary for SMC migration induced by PDGF and ECM proteins. The integrin or subunits responsible for facilitating migration varies with the stimulant. Agonists designed to inhibit integrin function might be used to suppress SMC migration and suppress the formation of intimal hyperplasia.

摘要

目的

平滑肌细胞(SMC)迁移是内膜增生过程的一个基本特征,内膜增生常常会限制血管重建的通畅性。本研究的目的是评估一系列整合素(即介导细胞黏附的细胞表面受体)对血小板衍生生长因子(PDGF)和细胞外基质(ECM)蛋白诱导的人SMC迁移的影响。

方法

采用免疫荧光染色法检测人隐静脉来源的SMC表面的各种整合素及其亚基。在存在或不存在阻断这些整合素功能的抗体的情况下,使用48孔微量趋化室检测SMC对各种基质蛋白和PDGF的趋化性和趋触性。

结果

在隐静脉SMC中鉴定出几种亚基(β1、α2、α5)和一种整合素(αvβ3)。β1整合素抗体抑制对I型和IV型胶原、层粘连蛋白和PDGF的趋化性。α2整合素抗体抑制I型和IV型胶原以及层粘连蛋白诱导的趋化性。α5整合素抗体对SMC迁移无影响。αvβ3整合素抗体抑制对PDGF的趋化性,但不抑制对ECM蛋白的趋化性。

结论

整合素是PDGF和ECM蛋白诱导的SMC迁移所必需的。促进迁移的整合素或亚基因刺激物而异。设计用于抑制整合素功能的激动剂可能用于抑制SMC迁移并抑制内膜增生的形成。

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