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首页> 外文期刊>Journal of Cellular Physiology >MicroRNA-21 represses human cystathionine gamma-lyase expression by targeting at specificity protein-1 in smooth muscle cells
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MicroRNA-21 represses human cystathionine gamma-lyase expression by targeting at specificity protein-1 in smooth muscle cells

机译：MicroRNA-21压制人类胱硫醚针对gamma-lyase表达式在平滑肌细胞特异性蛋白1

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摘要

Cystathionine gamma-lyase (CSE) is the major H 2S-generating enzyme in vascular smooth muscle cells (SMCs). CSE/H 2S system contributes to the maintenance of SMC phenotype, and transcript factor specificity protein-1 (SP1) is a critical regulator of CSE expression during SMC differentiation. The involvements of microRNA-21 (miR-21) in cardiovascular pathophysiology have been known, however miR-21 regulation of CSE and SP1 as well as SMC phenotype are uncertain. Using quantitative real-time PCR, we demonstrated that the expression of miR-21 was upregulated in dedifferentiated human aorta SMCs (HASMCs) and injured mouse carotid arteries. To determine the potential roles of miR-21 in SP1-mediated CSE gene expression and SMC phenotypic change, we showed that miR-21 expression was upregulated by miR-21 precursor. Interestingly, miR-21 overexpression significantly repressed the protein expressions of both CSE and SP1, inhibited H 2S production, stimulated SMC proliferation, and reduced SMC differentiation marker gene expression, respectively. The mRNA expression of CSE but not SP1 was inhibited by miR-21 precursor. Blockage of SP1 binding by mithramycin or inhibition of CSE activity by DL-propargylglycine did not change miR-21 expression. We further demonstrated that miR-21 repressed SP1 protein expression by directly targeting at SP1 3′ untranslational regions, which in turn downregulated CSE mRNA expression and stimulated SMC proliferation. Take together, these results suggest that miR-21 participates in CSE/H 2S-mediated-SMC differentiation by targeting SP1.
机译：胱硫醚gamma-lyase (CSE)是主要的H2在血管平滑肌s-generating酶细胞(smc)。维护SMC表型和成绩单因子特异性蛋白1 (SP1)是至关重要的监管机构在SMC CSE表达分化。(miR-21)在心血管病理生理学众所周知,然而miR-21 CSE和监管SP1 SMC表型是不确定的。定量实时PCR,我们证明了miR-21表达的调节肉瘤人类主动脉smc (HASMCs)和小鼠颈动脉受伤。潜在的角色的miR-21 SP1-mediated CSE基因表达和SMC表型改变,我们表明miR-21表达式被调节miR-21前体。超表达显著压抑蛋白质的表达CSE和SP1,抑制H 2 s生产,刺激了SMC扩散,减少了SMC分化分别标记基因表达。CSE的表达而不是抑制了SP1miR-21前体。光神霉素或抑制CSE活动DL-propargylglycine miR-21没有变化表达式。通过直接压抑SP1蛋白表达针对SP1 3 ' untranslational地区,进而表达下调CSE mRNA表达吗和刺激SMC增殖。这些结果表明,miR-21参与CSE / H 2 s-mediated-smc分化targeting SP1。

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