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首页> 外文期刊>Cellular Physiology and Biochemistry >Pressure Activates Src-Dependent FAK-Akt and ERK1/2 Signaling Pathways in Rat Hepatic Stellate Cells
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Pressure Activates Src-Dependent FAK-Akt and ERK1/2 Signaling Pathways in Rat Hepatic Stellate Cells

机译：压力激活大鼠肝星状细胞中Src依赖的FAK-Akt和ERK1 / 2信号通路。

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Background and Aims: Hepatic fibrosis is associated with elevated sinusoidal pressure, which can be transmitted to the hepatic stellate cells (HSCs) in the perisinusoidal space of Disse. Here, we sought to determine the effects of pressure on cellular growth and Src-dependent signaling pathways in the rat HSCs. Methods: Cultured rat HSCs were exposed to pressures (0 to 80 mmHg) by using a pressure-inducing apparatus. The proliferation of the cells was determined by a 5-bromo-2'-deoxy-uridine (BrdU) incorporation assay. Reverse transcription-PCR and Western-blot analysis were used to examine the mRNA and protein levels of representative molecules in Src-dependent signaling pathways. Results: Pressure at 10 to 20 mmHg applied to the HSCs over 1 h upregulated Brdu incorporation and expression of proliferating cell nuclear antigen (PCNA) and type I collagen, while a higher pressure of 40-80 mmHg did not have noticeable effect. The mRNA level of beta(3) integrin was increased by 1-h application of 5 to 20 mmHg. Immunoblot with phospho-specific antibodies demonstrated the phosphorylation of Src (Tyr418), focal adhesion kinase (FAK) (Tyr397), Akt (Ser473) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Thr421/Ser424) was increased in response to 10-mmHg pressure. Herbimycin A, an inhibitor of Src phosphorylation, attenuated the pressure-induced HSC proliferation and phosphorylation of above-mentioned signaling molecules. Conclusion: Our data demonstrated that pressure alone induced HSC proliferation involving the activation of Src-dependent signaling pathways.
机译：背景与目的：肝纤维化与正弦压力升高有关，正弦压力可以传播到Disse的正弦窦空间中的肝星状细胞（HSC）。在这里，我们试图确定压力对大鼠HSCs中细胞生长和Src依赖性信号通路的影响。方法：使用诱导装置将培养的大鼠HSC暴露于0至80 mmHg的压力下。通过5-溴-2'-脱氧尿苷（BrdU）掺入测定法确定细胞的增殖。逆转录PCR和蛋白质印迹分析用于检查Src依赖性信号通路中代表性分子的mRNA和蛋白水平。结果：在1 h内向HSC施加10至20 mmHg的压力上调了Brdu的掺入和增殖细胞核抗原（PCNA）和I型胶原的表达，而40-80 mmHg的较高压力没有明显的作用。通过施加1到5毫米汞柱的1小时，β（3）整合素的mRNA水平增加。用磷酸特异性抗体进行的免疫印迹表明Src（Tyr418），粘着斑激酶（FAK）（Tyr397），Akt（Ser473）以及细胞外信号调节激酶1和2（ERK1 / 2）（Thr421 / Ser424）的磷酸化增强响应10mmHg的压力。 Src磷酸化抑制剂除草霉素A减弱了压力诱导的HSC增殖和上述信号分子的磷酸化。结论：我们的数据表明，仅压力就诱导HSC增殖，涉及Src依赖性信号通路的激活。

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