• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >Reversal by growth hormone of homocysteine-induced epithelial-to- mesenchymal transition through membrane raft-redox signaling in podocytes
【24h】

Reversal by growth hormone of homocysteine-induced epithelial-to- mesenchymal transition through membrane raft-redox signaling in podocytes

机译：生长激素通过足细胞膜筏-氧化还原信号转导高半胱氨酸诱导的上皮-间充质转化

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

Epithelial-to-Mesenchymal Transition (EMT) is an important pathogenic mechanism mediating glomerular injury or sclerosis in a variety of renal and systemic diseases such as hyperhomocysteinemia (hHcys). The present study was designed to test whether Hcys-induced EMT in podocytes is reversed by growth hormone (GH), a hormone regulating cell differentiation and growth and to explore the cellular and molecular mechanism mediating its action. It was found that Hcys induced significant EMT in podocytes, as shown by marked decreases in slit diaphragm-associated protein P-cadherin and zonula occludens-1 as epithelial markers and by dramatic increases in the expression of mesenchymal markers, fibroblast specific protein-1 and α-smooth muscle actin, which were detected by all examinations via immunocytochemistry, real time RT-PCR and Western blot analysis. When podocytes were treated with GH at 25 ng/mL, however, Hcys failed to induce podocyte EMT. Using electromagnetic spin resonance spectrometry, Hcys-induced superoxide (O_2.~-) production via NADPH oxidase was found to be significantly inhibited by GH (66%). Functionally, GH was shown to substantially inhibit Hcys-induced increases in the permeability of podocyte monolayers and to block the decrease in podocin expression in these cells. In addition, NADPH oxidase subunit, gp91 ~(phox) and GH receptors aggregated in membrane raft clusters, which produced O_2.~- in response to Hcys and could be blocked by GH, membrane raft disruptors filipin and MCD or NADPH oxidase inhibitor, apocynin. It is concluded that Hcys-induced podocyte EMT is associated with transmembrane membrane raft-redox signaling and that GH reverses this Hcys-induced EMT protecting podocytes from functional disturbance.
机译：上皮-间充质转变（EMT）是介导肾小球损伤或硬化的重要致病机制，在多种肾脏和全身性疾病如高同型半胱氨酸血症（hHcys）中。本研究旨在测试Hcys诱导的足细胞EMT是否被生长激素（GH）（一种调节细胞分化和生长的激素）逆转，并探索介导其作用的细胞和分子机制。发现Hcys诱导足细胞中显着的EMT，如裂隙膜相关蛋白P-cadherin和zonula occludens-1作为上皮标记物显着减少以及间充质标记物，成纤维细胞特异性蛋白1和α-平滑肌肌动蛋白，通过免疫细胞化学，实时RT-PCR和Western印迹分析的所有检查均可检测到。但是，当用25 ng / mL GH处理足细胞时，Hcys无法诱导足细胞EMT。使用电磁自旋共振光谱法，发现通过NADPH氧化酶产生的Hcys诱导的超氧化物（O_2。〜-）被GH（66％）显着抑制。在功能上，GH显示出基本上抑制了Hcys诱导的足细胞单层通透性的增加，并阻止了这些细胞中podocin表达的减少。此外，NADPH氧化酶亚基，gp91〜（phox）和GH受体聚集在膜筏簇中，它们会响应Hcys产生O_2。〜-，并可能被GH，膜筏破坏者菲律宾血脂和MCD或NADPH氧化酶抑制剂，载脂蛋白。结论是Hcys诱导的足细胞EMT与跨膜筏筏氧化还原信号相关，并且GH逆转了Hcys诱导的EMT保护足细胞免受功能干扰。

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