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sean_zhang

银虫 (小有名气)

[求助] 求一个摘要的翻译

Matrix stiffening and myofibroblast resistance to apoptosis are cardinal features of chronic fibrotic diseases involving diverse organ systems. The interactions between altered tissue biomechanics and cellular signaling that sustain progressive fibrosis are not well defined. In this study, we used ex vivo and in vivo approaches to define a mechanotransduction pathway involving Rho/Rho kinase (Rho/ROCK), actin cytoskeletal remodeling, and a mechanosensitive transcription factor, megakaryoblastic leukemia 1 (MKL1), that coordinately regulate myofibroblast differentiation and survival. Both in an experimental mouse model of lung fibrosis and in human subjects with idiopathic pulmonary fibrosis (IPF), we observed activation of the Rho/ROCK pathway, enhanced actin cytoskeletal polymerization, and MKL1 cytoplasmic-nuclear shuttling. Pharmacologic disruption of this mechanotransduction pathway with the ROCK inhibitor fasudil induced myofibroblast apoptosis through a mechanism involving downregulation of BCL-2 and activation of the intrinsic mitochondrial apoptotic pathway. Treatment with fasudil during the postinflammatory fibrotic phase of lung injury or genetic ablation of Mkl1 protected mice from experimental lung fibrosis. These studies indicate that targeting mechanosensitive signaling in myofibroblasts to trigger the intrinsic apoptosis pathway may be an effective approach for treatment of fibrotic disorders.

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wxdlmc

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sean_zhang: 金币+4, 翻译EPI+1, 有帮助, 有一定的帮助,但是感觉有些是用翻译软件翻译的,不是很专业 2013-05-04 14:16:18
矩阵僵硬和肌成纤维细胞抗凋亡是慢性纤维化疾病涉及不同的器官系统的基本特征。改变组织的生物力学和细胞信号转导,维持肝纤维化进展都没有很好的定义之间的相互作用。在这项研究中,我们用体外和体内的方法来定义一个涉及Rho/Rho激酶信号转导通路(Rho/Rock),肌动蛋白细胞骨架重构,和一个机械的转录因子,巨核细胞白血病1(MKL1),协调规范肌成纤维细胞分化和存活。在实验性肺纤维化小鼠模型和人类受试者的特发性肺纤维化(IPF),我们观察到的Rho / ROCK信号通路的活化,增强的肌动蛋白细胞骨架的聚合,MKL1核质穿梭。与岩石抑制剂法舒地尔诱导细胞凋亡通过一种机制涉及的内在线粒体凋亡途径的激活,Bcl-2和下调这种转导途径的药物中断。实验性肺纤维化过程中肺损伤的保护小鼠的遗传消融或者MKL1的炎症后纤维化阶段,法舒地尔治疗。这些研究表明,靶向肌成纤维细胞离子信号触发内在的细胞凋亡通路可能为纤维化疾病治疗的一种有效的方法。
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