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首页> 外文期刊>Endothelium: Journal of endothelial cell research >Differential effects of shear stress and cyclic strain on Sp1 phosphorylation by protein kinase Czeta modulates membrane type 1-matrix metalloproteinase in endothelial cells.
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Differential effects of shear stress and cyclic strain on Sp1 phosphorylation by protein kinase Czeta modulates membrane type 1-matrix metalloproteinase in endothelial cells.

机译：剪切应力和循环应变对蛋白激酶Czeta的Sp1磷酸化的不同影响调节内皮细胞膜1型基质金属蛋白酶。

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摘要

Membrane type 1-matrix metalloproteinase (MT1-MMP) plays a key role in extracellular matrix remodeling, endothelial cell (EC) migration, and angiogenesis. Whereas cyclic strain (CS) increases MT1-MMP expression, shear stress (SS) decreases MT1-MMP expression. The aim of this study was to determine if changes in levels of Sp1 phosphorylation induced by protein kinase Czeta (PKCzeta) in ECs exposed to SS but not CS are important for MT1-MMP expression. The results showed that SS increased Sp1 phosphorylation, which could be inhibited by pretreatment with PKCzeta inhibitors. In the presence of PKCzeta inhibitors, the SS-mediated decrease in MT1-MMP protein expression was also abolished. These data demonstrate that increased affinity of Sp1 for MT1-MMP's promoter site occurs as a consequence of PKCzeta-induced phosphorylation of Sp1 in response to SS, increasing Sp1 binding affinity for the promoter site, preventing Egr-1 binding, and consequently decreasing MT1-MMP expression.
机译：膜1型基质金属蛋白酶（MT1-MMP）在细胞外基质重塑，内皮细胞（EC）迁移和血管生成中起关键作用。循环应变（CS）增加MT1-MMP表达，而剪切应力（SS）降低MT1-MMP表达。这项研究的目的是确定由蛋白激酶Czeta（PKCzeta）诱导的暴露于SS而不是CS的EC中的Sp1磷酸化水平的变化对于MT1-MMP表达是否重要。结果表明，SS增加了Sp1的磷酸化，这可以通过用PKCzeta抑制剂预处理来抑制。在PKCzeta抑制剂的存在下，SS介导的MT1-MMP蛋白表达的降低也被消除。这些数据表明，Sp1对MT1-MMP启动子位点的亲和力增加是由于PKCzeta响应于SS引起的Sp1磷酸化，增加了Sp1对启动子位点的结合亲和力，阻止了Egr-1结合，因此降低了MT1- MMP表达。

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