Fibronectin and vitronec tin induce AP-1-mediated matrix metalloproteinase-9 expression through integrin α5β1/αvβ3-dependent Akt, ERK and JNK signaling pathways in human umbilical vein endothelial cells
Fibronectin and vitronec tin induce AP-1-mediated matrix metalloproteinase-9 expression through integrin α5β1/αvβ3-dependent Akt, ERK and JNK signaling pathways in human umbilical vein endothelial cells
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DOI：
10.1016/j.cellsig.2010.08.012
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发表时间：
2011-01-01
影响因子：
4.8
通讯作者：
Lee, Hansoo
中科院分区：
文献类型：
--
作者：
Jin, Young-June;ParkA, Iha;Lee, Hansoo
基质金属蛋白酶（MMPs）选择性降解细胞外基质（ECM），其活性在血管生成中至关重要。相反，ECM组成/结构的变化会改变各种细胞类型中MMPs的表达和活性。在本研究中，我们研究了ECM成分的变化是否会影响内皮细胞MMPs的表达/活性，从而改变周围ECM的结构。在所检测的ECM分子中，纤连蛋白（FN）和玻璃体连接蛋白（VN）增加了人脐静脉内皮细胞（HUVECs）中MMP-9的表达和活性。α (5) β(1)和α (v) β(3)整合素都参与了fn诱导的MMP-9表达。此外，fn诱导的MMP-9表达是由AP-1转录因子介导的，包括c-Jun、JunB和JunD。AP-1激活信号转导的特异性抑制剂或sirna，包括FAK-Src、PI3K/Akt、ERK和JNK，可以抑制fn诱导的AP-1激活和MMP-9的表达。除了p38 MAPK外，vn诱导的AP-1激活和MMP-9表达也由这些AP-1激活信号转导介导。此外，FN或VN处理导致HUVEC培养板上胶原蛋白降解增加。综上所述，我们的数据表明，纤维连接蛋白和玻璃连接蛋白都通过内皮细胞中ap -1激活信号通路诱导MMP-9的表达，从而刺激周围胶原蛋白的降解，导致ECM结构的改变，并可能促进血管生成。(C) 2010爱思唯尔公司版权所有。
The activity of matrix metalloproteinases (MMPs), which selectively degrades the extracellular matrix (ECM), is critical in angiogenesis. Conversely, changes in ECM composition/structure alter the expression and activity of MMPs in various cell types. In the present study, we examined whether changes in ECM composition affect MMPs expression/activity of endothelial cells and thereby alter the surrounding ECM structure. Among the ECM molecules examined, fibronectin (FN) and vitronectin (VN) increased the expression and activity of MMP-9 in human umbilical vein endothelial cells (HUVECs). Both alpha(5)beta(1) and alpha(v)beta(3) integrins were involved in FN-induced MMP-9 expression. Also, FN-induced MMP-9 expression was found to be mediated by AP-1 transcription factors, including c-Jun, JunB, and JunD. Inhibitors or siRNAs specific to AP-1 activating signal transducers, including FAK-Src, PI3K/Akt, ERK, and JNK, abolished both FN-induced AP-1 activation and MMP-9 expression. VN-induced AP-1 activation and MMP-9 expression were also mediated by these AP-1 activating signal transducers in addition to p38 MAPK. Moreover, treatment with FN or VN resulted in increased degradation of collagen on HUVEC culture plates. Taken together, our data suggest that both fibronectin and vitronectin induce MMP-9 expression via the AP-1-activating signaling pathways in endothelial cells, and thereby stimulate degradation of surrounding collagen, leading to alterations in ECM structure and potentially the promotion of angiogenesis. (C) 2010 Elsevier Inc. All rights reserved.