整合素连接激酶对微血管平滑肌黏附和力学转导的调节。
Modulation of microvascular smooth muscle adhesion and mechanotransduction by integrin-linked kinase.
机构信息
Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, MO 65211, USA.
出版信息
Microcirculation. 2010 Feb;17(2):113-27. doi: 10.1111/j.1549-8719.2009.00011.x.
OBJECTIVE
In this study, we investigated the involvement of integrin-linked kinase (ILK) in the adhesion of arteriolar vascular smooth muscle cells (VSMC) to fibronectin (FN) and in the mechano-responsiveness of VSMC focal adhesions (FA).
METHODS
ILK was visualized in VSMC by expressing EGFP-ILK and it was knocked down using ILK-shRNA constructs. Atomic force microscopy (AFM) was used to characterize VSMC interactions with FN, VSMC stiffness and to apply and measure forces at a VSMC single FA site.
RESULTS
ILK was localized to FA and silencing ILK promoted cell spreading, enhanced cell adhesion, reduced cell proliferation and reduced downstream phosphorylation of GSK-3beta and PKB/Akt. AFM studies demonstrated that silencing ILK enhanced alpha5beta1 integrin adhesion to FN and enhanced VSMC contraction in response to a pulling force applied at the level of a single FN-FA site.
CONCLUSIONS
ILK functions in arteriolar VSMC appear linked to multiple signaling pathways and processes that inhibit cell spreading, cell adhesion, FA formation, adhesion to FN and the mechano-responsiveness of FN-FA sites.
目的
在这项研究中，我们研究了整合素连接激酶（ILK）在小动脉血管平滑肌细胞（VSMC）与纤维连接蛋白（FN）黏附以及 VSMC 黏附点（FA）的力学反应中的作用。
方法
通过表达 EGFP-ILK 来显示 ILK 在 VSMC 中的定位，并使用 ILK-shRNA 构建物进行敲低。原子力显微镜（AFM）用于表征 VSMC 与 FN 的相互作用、VSMC 的刚性以及在 VSMC 单个 FA 部位施加和测量力。
结果
ILK 定位于 FA，沉默 ILK 促进细胞铺展，增强细胞黏附，减少细胞增殖，并减少 GSK-3β 和 PKB/Akt 的下游磷酸化。AFM 研究表明，沉默 ILK 增强了 alpha5beta1 整合素与 FN 的黏附，并增强了 VSMC 对单个 FN-FA 部位施加的拉力的收缩反应。
结论
ILK 在小动脉 VSMC 中的功能似乎与多个信号通路和过程有关，这些信号通路和过程抑制细胞铺展、细胞黏附、FA 形成、FN 黏附以及 FN-FA 部位的力学反应。
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