...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >Role of Protease-Activated Receptor 2 in Regulating Focal Segmental Glomerulosclerosis
【24h】

Role of Protease-Activated Receptor 2 in Regulating Focal Segmental Glomerulosclerosis

机译：蛋白酶激活受体2在调节局部节段性肾小球硬化中的作用

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

>Background /Aims: The underlying mechanisms leading to focal segmental glomerulosclerosis (FSGS) are lacking. In this report, we examined the role of protease-activated receptors (PARs) subtype PAR2 and its downstream signals in regulating the pathophysiological process of FSGS. Methods: Nephropathy was induced by intravenous injections of adriamycin (ADR) in rats to study FSGS. Western Blot analysis and ELISA were employed to determine the protein expression levels of PAR2 and its downstream signal pathways as well as the levels of PICs. Results: In ADR rats, expression of PAR2, PKC?μ and PKA was amplified and this was accompanied with increases of pro-inflammatory cytokines (PICs) including IL-1?2, IL-6 and TNF-?±. Inhibition of PAR2 signal by systemic administration of FSLLRY-NH2 (FSL) attenuated amplification of PICs. Notably, FSL further influenced key molecular mediators during development of FSGS. i.e., it specifically restored the impaired nephrin and attenuated the exaggerated transforming growth factor beta 1 (TGF-?21), caspase-9 and desmin thereby improving worsened renal functions and glomerular injury. Consistent with this, in cultured podocytes FSL also largely restored downregulation of nephrin and attenuated amplifications of caspase-9 and desmin induced by TGF-?21. Conclusions: Results of this study suggest that PAR2 plays an important role in mediating renal injury induced by glomerulosclerosis. Inhibition of PAR2 signal pathway has a protective effect on FSGS mainly via PIC and TGF-?21 mechanisms. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of FSGS observed in patients.
机译：> 背景/目的： 尚缺乏导致局灶性节段性肾小球硬化症（FSGS）的潜在机制。在本报告中，我们研究了蛋白酶激活受体（PARs）PAR2亚型及其下游信号在调节FSGS病理生理过程中的作用。 方法： 通过静脉内注射阿霉素（ADR）诱导大鼠肾病以研究FSGS。 Western Blot分析和ELISA用于确定PAR2的蛋白表达水平及其下游信号通路以及PICs的水平。 结果： 在ADR大鼠中，PAR2，PKC？μ和PKA的表达被扩增，并伴随着包括IL-1？在内的促炎细胞因子（PIC）的增加。 2，IL-6和TNF-α±。通过全身施用FSLLRY-NH2（FSL）来抑制PAR2信号，从而使PIC的扩增减弱。值得注意的是，FSL在FSGS的开发过程中进一步影响了关键分子介体。即，它特异性地恢复了受损的肾素，并减弱了夸大的转化生长因子β1（TGF-β21），caspase-9和结蛋白，从而改善了恶化的肾功能和肾小球损伤。与此相一致，在培养的足细胞中，FSL还很大程度上恢复了肾素的下调，并减弱了TGF-β21诱导的caspase-9和结蛋白的扩增。 结论： 该研究结果表明PAR2在介导肾小球硬化引起的肾损伤中起重要作用。抑制PAR2信号通路主要通过PIC和TGF-β21机制对FSGS具有保护作用。靶向这些信号分子中的一个或多个可能为治疗和管理在患者中观察到的FSGS提供新的机会。

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