Integrin expression and function in the response of primary culture hepatic stellate cells to connective tissue growth factor (CCN2).
Integrin expression and function in the response of primary culture hepatic stellate cells to connective tissue growth factor (CCN2).
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DOI：
10.1111/j.1582-4934.2010.01072.x
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发表时间：
2011-05
影响因子：
5.3
通讯作者：
Brigstock DR
中科院分区：
文献类型：
--
作者：
Huang G;Brigstock DR
结缔组织生长因子（CCN 2，也称为CTGF）的产生是肝纤维化的标志。本研究检查了肝星状细胞（HSC）的早期原代培养物（i）CCN 2对其同源受体整联蛋白亚基的调节;以及（ii）CCN 2与整联蛋白α5β1、硫酸乙酰肝素蛋白聚糖（HSPG）或纤连蛋白（FN）之间在支持细胞粘附方面的相互作用。从健康雄性Balb/c小鼠中分离HSC。在第1-7天原代培养的HSC中以及用重组CCN 2或CCN 2小干扰RNA处理的第3天或第7天的细胞中测量CCN 2或α5、β1、αv或β3整联蛋白亚基的mRNA水平。使用体外细胞粘附试验研究了CCN 2与整合素α5β1、HSPG或FN之间的相互作用。与前7天的自主激活同时发生，原代培养的HSC越来越多地表达CCN 2或整合素亚基的mRNA。添加外源性CCN 2或敲低内源性CCN 2差异调节第3天与第7天细胞中的整合素基因表达。全长CCN 2（“CCN 21 - 4”）或仅含有模块4的残基247-349（“CCN 24”）以整联蛋白α5β1和HSP依赖性方式支持第3天细胞粘附。CCN 21 -4或CCN 24以整合素α5β1依赖性方式促进第3天细胞与FN的粘附，而FN促进HSP G依赖性HSC与CCN 21 -4或CCN 24的粘附。这些发现表明CCN 2调节原代培养HSC中的整合素表达，并通过其与细胞表面整合素α5β1的结合支持HSC粘附，α 5β1是原代培养HSC中与HSPG或FN协同相互作用的新型CCN 2受体。
Production of connective tissue growth factor (CCN2, also known as CTGF) is a hallmark of hepatic fibrosis. This study examined early primary cultures of hepatic stellate cells (HSC) for (i) CCN2 regulation of its cognate receptor integrin subunits; and (ii) interactions between CCN2 and integrin α5β1, heparan sulphate proteoglycans (HSPG) or fibronectin (FN) in supporting cell adhesion. HSC were isolated from healthy male Balb/c mice. mRNA levels of CCN2 or α5, β1, αv or β3 integrin subunits were measured in days 1–7 primary culture HSC, and day 3 or day 7 cells treated with recombinant CCN2 or CCN2 small interfering RNA. Interactions between CCN2 and integrin α5β1, HSPG or FN were investigated using an in vitro cell adhesion assay. Co-incident with autonomous activation over the first 7 days, primary culture HSC increasingly expressed mRNA for CCN2 or integrin subunits. Addition of exogenous CCN2 or knockdown of endogenous CCN2 differentially regulated integrin gene expression in day 3 versus day 7 cells. Either full length CCN2 (‘CCN21–4’) or residues 247–349 containing module 4 alone (‘CCN24’) supported day 3 cell adhesion in an integrin α5β1- and HSPG-dependent fashion. Adhesion of day 3 cells to FN was promoted in an integrin α5β1-dependent manner by CCN21–4 or CCN24, whereas FN promoted HSPG-dependent HSC adhesion to CCN21–4 or CCN24. These findings suggest CCN2 regulates integrin expression in primary culture HSC and supports HSC adhesion via its binding of cell surface integrin α5β1, a novel CCN2 receptor in primary culture HSC which interacts co-operatively with HSPG or FN.
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影响因子：
25.7
作者：
Milliano, MT;Luxon, BA
通讯作者：
Luxon, BA
影响因子：
4.1
作者：
Leask, Andrew;Chen, Shaoqiong;Brigstock, David R.
通讯作者：
Brigstock, David R.
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24.5
作者：
Gao, R.;Brigstock, D. R.
通讯作者：
Brigstock, D. R.
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3.5
作者：
Hoshijima, M;Hattori, T;Takigawa, M
通讯作者：
Takigawa, M
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5
作者：
Paradis, V;Dargere, D;Bedossa, P
通讯作者：
Bedossa, P