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首页> 外文期刊>Parasitology >TGF-beta receptor type II costameric localization in cardiomyocytes and host cell TGF-beta response is disrupted by Trypanosoma cruzi infection
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TGF-beta receptor type II costameric localization in cardiomyocytes and host cell TGF-beta response is disrupted by Trypanosoma cruzi infection

机译:克鲁格氏锥虫感染破坏了心肌细胞和宿主细胞TGF-β反应中的TGF-β受体II型肋骨定位

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Transforming growth factor beta (TGF-beta) cytokine is involved in Chagas disease establishment and progression. Since Trypanosoma cruzi can modulate host cell receptors, we analysed the TGF-beta receptor type II (T beta RII) expression and distribution during T. cruzi - cardiomyocyte interaction. T beta RII immunofluorescent staining revealed a striated organization in cardiomyocytes, which was co-localized with vinculin costameres and enhanced (38%) after TGF-beta treatment. Cytochalasin D induced a decrease of 45.3% in the ratio of cardiomyocytes presenting T beta RII striations, demonstrating an association of T beta RII with the cytoskeleton. Western blot analysis showed that cytochalasin D significantly inhibited Smad 2 phosphorylation and fibronectin stimulation after TGF-beta treatment in cardiomyocytes. Trypanosoma cruzi infection elicited a decrease of 79.8% in the frequency of cardiomyocytes presenting T beta RII striations, but did not interfere significantly in its expression. In addition, T. cruzi-infected cardiomyocytes present a lower response to exogenous TGF-beta, showing no enhancement of T beta RII striations and a reduction of phosphorylated Smad 2, with no significant difference in T beta RII expression when compared to uninfected cells. Together, these results suggest that the co-localization of T beta RII with costameres is important in activating the TGF-beta signalling cascade, and that T. cruzi-derived cytoskeleton disorganization could result in altered or low TGF-beta response in infected cardiomyocytes.
机译:转化生长因子β(TGF-β)细胞因子参与恰加斯病的建立和发展。由于克氏锥虫可以调节宿主细胞受体,因此我们分析了克氏锥虫-心肌细胞相互作用期间TGF-β受体II型(T beta RII)的表达和分布。 T beta RII免疫荧光染色显示出心肌细胞中的横纹组织,该组织与新蛋白椰油共定位,并在TGF-beta治疗后增强(38%)。细胞松弛素D诱导呈现T beta RII条纹的心肌细胞比例下降45.3%,表明T beta RII与细胞骨架相关。蛋白质印迹分析表明,在心肌细胞中TGF-β处理后,细胞松弛素D显着抑制Smad 2磷酸化和纤连蛋白刺激。克氏锥虫感染引起呈现TβRII条纹的心肌细胞的频率降低了79.8%,但并未明显干扰其表达。此外,被克鲁斯氏菌感染的心肌细胞对外源性TGF-β的响应较低,与未感染的细胞相比,TβRII的条纹没有增强,磷酸化的Smad 2也没有减少,T beta RII的表达没有显着差异。在一起,这些结果表明,T beta RII与肋骨的共定位在激活TGF-beta信号级联中很重要,而T. cruzi衍生的细胞骨架紊乱可能导致感染的心肌细胞中TGF-beta响应改变或降低。

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