Integrin-linked kinase regulates migration and proliferation of human intestinal cells under a fibronectin-dependent mechanism.
Integrin-linked kinase regulates migration and proliferation of human intestinal cells under a fibronectin-dependent mechanism.
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DOI：
10.1002/jcp.21963
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发表时间：
2010-02
影响因子：
5.6
通讯作者：
Beaulieu, Jean-Francois
中科院分区：
文献类型：
--
作者：
Gagne, David;Groulx, Jean-Francois;Benoit, Yannick D.;Basora, Nuria;Herring, Elizabeth;Vachon, Pierre H.;Beaulieu, Jean-Francois
整合素连接激酶（ILK）在整合素信号传导介导的细胞外基质（ECM）-细胞相互作用中起作用，并且还在功能性粘着斑中充当支架蛋白。在本研究中，我们研究了ILK在人肠上皮细胞（IEC）在体内和体外的表达和作用。在本文中，我们报道了ILK及其支架功能相互作用伴侣PINCH-1、α-parvin和β-parvin根据从隐窝（增殖/未分化）室底部到绒毛（非增殖/分化）室顶部的递减梯度表达，紧密遵循ECM/基底膜组分纤连蛋白的表达模式。人IEC中ILK的siRNA敲低导致PINCH-1、α-parvin和β-parvin表达的丧失，沿着细胞增殖的显著降低，这是由于细胞周期蛋白D1的丧失以及p27和低磷酸化pRb表达水平的增加。ILK敲低严重影响细胞的扩散、迁移和恢复能力，这与纤连蛋白沉积的减少直接相关。所有ILK敲低诱导的缺陷都用外源沉积的纤连蛋白挽救。总之，我们的研究结果表明，ILK在控制人肠细胞和隐窝绒毛轴的稳态，特别是关于基底膜纤维连接蛋白沉积，以及细胞增殖，扩散和迁移中起着至关重要的作用。J.细胞。222：387-400，2010。© 2009 Wiley-Liss公司。
Integrin-linked kinase (ILK) plays a role in integrin signaling-mediated extracellular matrix (ECM)–cell interactions and also acts as a scaffold protein in functional focal adhesion points. In the present study, we investigated the expression and roles of ILK in human intestinal epithelial cells (IECs) in vivo and in vitro. Herein, we report that ILK and its scaffold-function interacting partners, PINCH-1, α-parvin, and β-parvin, are expressed according to a decreasing gradient from the bottom of the crypt (proliferative/undifferentiated) compartment to the tip of the villus (non-proliferative/differentiated) compartment, closely following the expression pattern of the ECM/basement membrane component fibronectin. The siRNA knockdown of ILK in human IECs caused a loss of PINCH-1, α-parvin, and β-parvin expression, along with a significant decrease in cell proliferation via a loss of cyclin D1 and an increase in p27 and hypophosphorylated pRb expression levels. ILK knockdown severely affected cell spreading, migration, and restitution abilities, which were shown to be directly related to a decrease in fibronectin deposition. All ILK knockdown-induced defects were rescued with exogenously deposited fibronectin. Altogether, our results indicate that ILK performs crucial roles in the control of human intestinal cell and crypt–villus axis homeostasis—especially with regard to basement membrane fibronectin deposition—as well as cell proliferation, spreading, and migration. J. Cell. Physiol. 222: 387–400, 2010. © 2009 Wiley-Liss, Inc.
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影响因子：
4.1
作者：
BEAULIEU, JF;QUARONI, A
通讯作者：
QUARONI, A
影响因子：
29.4
作者：
BEAULIEU, JF;VACHON, PH
通讯作者：
VACHON, PH
DOI：
10.1152/ajpgi.1996.271.5.g729
发表时间：
1996-11-01
影响因子：
4.5
作者：
Goke, M;Zuk, A;Podolsky, DK
通讯作者：
Podolsky, DK
影响因子：
6
作者：
Guo, LD;Sanders, PW;Wu, CY
通讯作者：
Wu, CY
影响因子：
6.1
作者：
Basson, MD
通讯作者：
Basson, MD