首页> 外文期刊>Regulatory peptides. >Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells.
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Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells.

机译:血管紧张素II通过核因子-κB依赖性途径在血管平滑肌细胞中诱导基质金属蛋白酶9表达。

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摘要

Angiotensin II (AngII) is widely recognized as a critical regulator of the development of atherosclerosis. Matrix metalloproteinases (MMPs) are thought to participate in plaque destabilization through degradation of the extracellular matrix. In the present study, we investigated the potential mechanism of AngII-induced MMP-9 expression in vascular smooth muscle cells (VSMC). AngII upregulated the expression of MMP-9 significantly in VSMC obtained from rat aorta. RNAi-mediated knockdown of p65 and losartan, an inhibitor of AngII receptors subtype-1 (AT1), could abolish AngII-induced MMP-9 expression. In addition, AngII induced the NF-kappaB binding activity via AT1 and AT2 receptors in VSMC, and AngII-induced activation of NF-kappaB is not associated with significant downregulation of IkappaB. In summary, this study demonstrates that AngII stimulates NF-kappaB nuclear translocation in VSMC via AT1 and AT2. AngII increases the expression of MMP-9 in VSMC, and AT1 and NF-kappaB pathways have an important role in this response.
机译:血管紧张素II(AngII)被广泛认为是动脉粥样硬化发展的关键调节剂。基质金属蛋白酶(MMP)被认为通过降解细胞外基质而参与了斑块失稳。在本研究中,我们调查了血管平滑肌细胞(VSMC)中AngII诱导的MMP-9表达的潜在机制。 AngII上调了大鼠主动脉VSMC中MMP-9的表达。 RNAi介导的p65和losartan(一种AngII受体亚型1(AT1)的抑制剂)的敲除可废除AngII诱导的MMP-9表达。此外,AngII通过VSMC中的AT1和AT2受体诱导NF-kappaB结合活性,并且AngII诱导的NF-kappaB激活与IkappaB的显着下调无关。总而言之,这项研究表明,AngII通过AT1和AT2刺激VSMC中的NF-κB核易位。 AngII增加了VSMC中MMP-9的表达,而AT1和NF-kappaB途径在该反应中起重要作用。

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