...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Translational research: the journal of laboratory and clinical medicine >Lovastatin inhibits oxidized low-density lipoprotein-induced plasminogen activator inhibitor and transforming growth factor-beta1 expression via a decrease in Ras/extracellular signal-regulated kinase activity in mesangial cells.
【24h】

Lovastatin inhibits oxidized low-density lipoprotein-induced plasminogen activator inhibitor and transforming growth factor-beta1 expression via a decrease in Ras/extracellular signal-regulated kinase activity in mesangial cells.

机译：洛伐他汀通过抑制肾小球系膜细胞中Ras /细胞外信号调节激酶的活性，抑制氧化的低密度脂蛋白诱导的纤溶酶原激活剂抑制剂并转化生长因子-β1表达。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Oxidized low-density lipoprotein (Ox-LDL) might be involved in the progression of renal disease. Ox-LDL stimulation of plasminogen activator inhibitor-1 (PAI-1) expression via transforming growth factor-beta (TGF-beta)/Smad signaling in mesangial cells required activation of extracellular signal-regulated kinase (ERK). Mevalonate depletion by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, decreases the levels of farnesyl pyrophosphate (FPP) for isoprenylation of Ras. We postulate that statins may ameliorate the Ox-LDL-induced mesangial matrix accumulation by inhibiting Ras/ERK activation with subsequent downregulation of TGF-beta target genes. Quiescent mesangial cells were incubated for 18 h with and without the presence of lovastatin before 50 microg/mL of Ox-LDL treatment for 1 h. Lovastatin inhibited markedly the stimulatory effects of Ox-LDL on ERK1/2 activation, nuclear Smad3 expression, TGF-beta1 and PAI-1 mRNA and protein expression, and PAI-1 luciferase activity. These inhibitory effects of lovastatin were reversed almost completely by mevalonate or FPP. Similar to lovastatin, FTI-277, which is an inhibitor of Ras farnesylation, decreased the Ox-LDL-induced activation of ERK/Smad3 and induction of TGF-beta1/PAI-1. These results indicate that lovastatin prevents the Ox-LDL-induced Ras/ERK activation that results in inhibition of Smad3 activation in mesangial cells with subsequent downregulation of TGF-beta target genes. Thus, statins seem to have antifibrotic effects through their anti-TGF-beta response that are relevant in the treatment of chronic renal disease with dyslipidemia.
机译：氧化型低密度脂蛋白（Ox-LDL）可能与肾脏疾病的进展有关。通过肾小球系膜细胞中转化生长因子-β（TGF-beta）/ Smad信号转导的血纤维蛋白溶酶原激活物抑制剂1（PAI-1）表达的Ox-LDL刺激需要激活细胞外信号调节激酶（ERK）。 3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂或他汀类药物引起的甲羟戊酸消耗减少了Ras异戊二烯化的法呢基焦磷酸酯（FPP）的水平。我们推测他汀类药物可通过抑制Ras / ERK激活并随后下调TGF-beta目标基因来改善Ox-LDL诱导的系膜基质积聚。在有洛伐他汀存在和不存在洛伐他汀的情况下，将静止的肾小球膜细胞孵育18小时，然后以50μg/ mL的Ox-LDL处理1小时。洛伐他汀显着抑制Ox-LDL对ERK1 / 2活化，核Smad3表达，TGF-beta1和PAI-1 mRNA和蛋白表达以及PAI-1荧光素酶活性的刺激作用。洛伐他汀的这些抑制作用被甲羟戊酸或FPP几乎完全逆转。与洛伐他汀相似，作为Ras法呢基化抑制剂的FTI-277降低了Ox-LDL诱导的ERK / Smad3激活和TGF-beta1 / PAI-1的诱导。这些结果表明，洛伐他汀可以阻止Ox-LDL诱导的Ras / ERK激活，从而抑制系膜细胞中Smad3的激活，并随后下调TGF-beta靶基因。因此，他汀类药物似乎通过其抗TGF-β反应具有抗纤维化作用，与治疗血脂异常的慢性肾脏疾病有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号