Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells
Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells
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DOI：
10.1074/jbc.m111213200
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发表时间：
2002-03-22
影响因子：
4.8
通讯作者：
Karnovsky, MJ
中科院分区：
文献类型：
--
作者：
Fan, WH;Karnovsky, MJ
结缔组织生长因子（CTGF）在动脉粥样硬化病变的血管平滑肌细胞（VSMC）中大量表达，而在正常血管中不表达。CTGF能促进VSMC增殖和迁移，影响细胞外基质的组成。控制这些事件的机制尚不清楚。我们研究了CTGF对基质金属蛋白酶（MMPs）的影响，通过将CTGF过表达构建体导入VSMC。我们发现CTGF的过表达显著增加了VSMC条件培养液中MMP-2的活性。MMP-2的活性增加类似的外源性CTGF治疗，这种效果可以被阻断的抗CTGF抗体。我们还发现，MMP-2活性的增加是由于MMP-2 mRNA水平的增加，在VSMC。我们进一步研究了MMP-2 mRNA水平的调控机制，发现AP-2转录因子负责CTGF诱导的MMP-2转录的大部分。由于MMP-2是直接参与控制细胞运动和细胞外基质周转的重要因子，我们的研究可能提供CTGF促进VSMC迁移的机制。
Connective tissue growth factor (CTGF) is abundantly expressed in the vascular smooth muscle cells (VSMC) of atherosclerotic lesions but not in normal vessels. CTGF is able to promote VSMC proliferation and migration and influences the composition of extracellular matrix. The mechanisms for controlling these events remain unclear. We studied the effects of CTGF on matrix metalloproteinases (MMPs) by introducing a CTGF overexpression construct into VSMC. We found that the over-expression of CTGF significantly increased the activity of MMP-2 in VSMC conditioned medium. MMP-2 activity was similarly increased by exogenous CTGF treatment, and this effect could be blocked by an anti-CTGF antibody. We also showed that the increased MMP-2 activity was due to an increase in MMP-2 mRNA levels in VSMC. We further studied the mechanisms involved in the regulation of MMP-2 mRNA levels and found that the AP-2 transcription factor is responsible for most of the CTGF-induced MMP-2 transcription. Because MMP-2 is an important factor directly involved in controlling cell movement and the turnover of extracellular matrix, our study may provide a mechanism for CTGF-promoted VSMC migration.