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首页> 外文期刊>Journal of Cellular Physiology >IL-6 Activates PI3K and PKC zeta Signaling and Determines Cardiac Differentiation in Rat Embryonic H9c2 Cells
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IL-6 Activates PI3K and PKC zeta Signaling and Determines Cardiac Differentiation in Rat Embryonic H9c2 Cells

机译:il - 6激活PI3K和PKCζ信号决定在大鼠心脏分化胚胎H9c2细胞

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Introduction: IL-6 influences several biological processes, including cardiac stem cell and cardiomyocyte physiology. Although JAK-STAT3 activation is the defining feature of IL-6 signaling, signaling molecules such as PI3K, PKCs, and ERK1/2 are also activated and elicit different responses. Moreover, most studies on the specific role of these signaling molecules focus on the adult heart, and few studies are available on the biological effects evoked by IL-6 in embryonic cardiomyocytes. Aim: The aim of this study was to clarify the biological response of embryonic heart derived cells to IL-6 by analyzing the morphological modifications and the signaling cascades evoked by the cytokine in H9c2 cells. Results: IL-6 stimulation determined the terminal differentiation of H9c2 cells, as evidenced by the increased expression of cardiac transcription factors (NKX2.5 and GATA4), structural proteins (-myosin heavy chain and cardiac Troponin T) and the gap junction protein Connexin 43. This process was mediated by the rapid modulation of PI3K, Akt, PTEN, and PKC phosphorylation levels. PI3K recruitment was an upstream event in the signaling cascade and when PI3K was inhibited, IL-6 failed to modify PKC, PTEN, and Akt phosphorylation. Blocking PKC activity affected only PTEN and Akt. Finally, the overexpression of a constitutively active form of PKC in H9c2 cells largely mimicked the morphological and molecular effects evoked by IL-6. Conclusions: This study demonstrated that IL-6 induces the cardiac differentiation of H9c2 embryonic cells though a signaling cascade that involves PI3K, PTEN, and PKC activities. J. Cell. Physiol. 231: 576-586, 2016. (c) 2015 Wiley Periodicals, Inc.
机译:作品简介:il - 6的影响几个生物流程,包括心脏干细胞和心肌细胞生理机能。激活的定义特征是il - 6PI3K等信号,信号分子,PKCs, ERK1/2也激活并引起不同的反应。这些信号分子的特定角色关注成人心脏,和一些研究可用的生物效应引起的在胚胎心肌细胞il - 6。本研究旨在阐明生物反应胚胎心脏衍生细胞il - 6形态分析和修改信号级联H9c2诱发的细胞因子细胞。H9c2终端分化的细胞证明了增加心脏的表达式转录因子(NKX2.5和GATA4),结构蛋白(肌凝蛋白重链和心肌肌钙蛋白T)和缝隙连接蛋白联接蛋白43。PI3K的快速调制,Akt、PTEN和PKC磷酸化水平。信号级联,当上游事件抑制PI3K, il - 6修改PKC失败,PTEN和一种蛋白激酶磷酸化。活动只有PTEN和Akt的影响。过度的既定的活动形式H9c2细胞中PKC很大程度上模仿了形态学和分子效应诱发的il - 6的分泌。il - 6产生H9c2的心脏分化胚胎细胞虽然信号级联包括PI3K、PTEN和PKC活动。杂志。231:576 - 586年,2016年。期刊、公司。

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