...
首页> 外文期刊>Journal of Cellular Physiology >Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2
【24h】

Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2

机译:干扰素-γ促进血管重建人类微血管内皮细胞移植内皮素(ET) 1和转化生长因子

获取原文
获取原文并翻译 | 示例
           

摘要

Systemic sclerosis (SSc) is a complex disease characterized by vascular alterations, activation of the immune system and tissue fibrosis. Previous studies have implicated activation of the interferon pathways in the pathogenesis of SSc. The goal of this study was to determine whether interferon type I and/or type II could play a pathogenic role in SSc vasculopathy. Human dermal microvascular endothelial cells (HDMVECs) and fibroblasts were obtained from foreskins of healthy newborns. The RT Profiler PCR Array System was utilized to screen for EndoMT genes. Treatment with IFN-α or IFN-γ downregulated Fli1 and VE-cadherin. In contrast, IFN-α and IFN-γ exerted opposite effects on the expression of α-SMA, CTGF, ET-1, and TGFβ2, with IFN-α downregulating and IFN-γ upregulating this set of genes. Blockade of TGFβ signaling normalized IFN-γ-mediated changes in Fli1, VE-cadherin, CTGF, and ET-1 levels, whereas upregulation of α-SMA and TGFβ2 was not affected. Bosentan treatment was more effective than TGFβ blockade in reversing the actions of IFN-γ, including downregulation of α-SMA and TGFβ2, suggesting that activation of the ET-1 pathway plays a main role in the IFN-γ responses in HDMECs. IFN-γ induced expression of selected genes related to endothelial-to-mesenchymal transition (EndoMT), including Snail1, FN1, PAI1, TWIST1, STAT3, RGS2, and components of the WNT pathway. The effect of IFN-γ on EndoMT was mediated via TGFβ2 and ET-1 signaling pathways. This study demonstrates distinct effects of IFN-α and IFN-γ on the biology of vascular endothelial cells. IFN-γ may contribute to abnormal vascular remodeling and fibrogenesis in SSc, partially via induction of EndoMT.
机译:系统性硬化症(SSc)是一种复杂的疾病特点是血管改变,激活免疫系统和组织纤维化。先前的研究已经涉及激活的干扰素通路的发病机理SSc。干扰素I型和II型是否可以发挥致病作用SSc血管病变。皮肤微血管内皮细胞(HDMVECs)和成纤维细胞从包皮中获得的健康的新生儿。系统利用屏幕EndoMT基因。治疗干扰素-α或干扰素-γFli1使之抑制和VE-cadherin。产生相反效果的表达αsma, CTGF、ET-1 TGFβ2,与干扰素-α表达下调和干扰素-γ移植这组基因。干扰素-γ介导的变化Fli1 VE-cadherin,CTGF和ET-1水平,而upregulationαsma TGFβ2并没有受到影响。比TGFβ封锁的治疗更有效在扭转干扰素-γ的行为,包括downregulationα的sma和TGFβ2,暗示ET-1通路的激活起着主要作用在干扰素-γHDMECs反应。选择基因的诱导表达有关endothelial-to-mesenchymal过渡(EndoMT),包括Snail1、FN1 PAI1 TWIST1, STAT3, RGS2,和组件的WNT通路。干扰素-γEndoMT是通过转化生长因子β2和ET-1介导信号通路。不同的影响干扰素-α和干扰素-γ的血管内皮细胞的生物学。导致血管重塑和异常通过诱导纤维发生在SSc,部分

著录项

相似文献

  • 外文文献
  • 中文文献
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