ELife:microRNA-122在肝细胞抗病毒天然免疫中的作用

2019-03-30 佚名 中山大学生科院

近日,国际著名生物学综合期刊eLife上发表了中山大学生命科学学院屈良鹄教授课题组的最新研究成果“MicroRNA-122 supports robust innate immunity in hepatocytes by targeting the RTKs/STAT3 signaling pathway”。该论文首次报道了肝脏特异性的小分子非编码核糖核酸microRNA-122在肝细胞抗病毒天

近日,国际著名生物学综合期刊eLife上发表了中山大学生命科学学院屈良鹄教授课题组的最新研究成果“MicroRNA-122 supports robust innate immunity in hepatocytes by targeting the RTKs/STAT3 signaling pathway”。该论文首次报道了肝脏特异性的小分子非编码核糖核酸microRNA-122在肝细胞抗病毒天然免疫中的重要作用,并揭示microRNA-122通过抑制RTK/STAT3信号通路赋予肝细胞强有力天然免疫功能的核心机制。


miR-122调控STAT3磷酸化及干扰素反应的机制示意图

固有天然免疫反应(Intrinsic innate immune responses)是我们体内每一种细胞都具有的抵抗病毒等病原体侵害的天然免疫防御功能。由于它是一切免疫应答的基础,因此也被称为免疫的第一道防线。不同类型的细胞,特别是上皮细胞中天然免疫的生成及其调控目前并不清楚。microRNA-122是肝细胞中特异性高丰度表达的微小RNA分子,而在肝癌细胞中表达显着下调或者缺失。屈良鹄教授课题组发现:在肝癌细胞HepG2中导入microRNA-122可以极其显着地增强细胞应对各种病毒核酸(包括HCV和HBV)的天然免疫反应。研究发现microRNA-122可以直接靶向多种受体酪氨酸激酶(RTK),从而降低了HepG2细胞中STAT3的酪氨酸磷酸化水平。更有趣的是,他们发现STAT3可以直接抑制干扰素调节因子IRF1的表达,STAT3酸磷酸化水平的下调解除了STAT3对干扰素转录激活的抑制,从而使得干扰素信号通路在病原体入侵时能迅猛激活。该研究揭示了在肝细胞中miR-122–RTKs/STAT3–IRF1–IFNs通路调控干扰素表达的重要途径,阐明了微RNA对肝细胞等非免疫细胞天然免疫能力调控的新机制。

成熟肝细胞中microRNA-122表达量极其丰富,因此在遇到病毒侵害时可迅速启动天然免疫应答,这种强健的天然免疫能力对于肝细胞是必不可少的,一旦肝细胞中microRNA-122含量不足(比如,病毒感染引起的炎症可导致microRNA-122表达下调),就会导致肝细胞天然免疫能力大幅下降,更容易被病毒入侵。以上这些发现对于病毒慢性感染引起的肝脏疾病,特别是癌症的治疗具有重要指导意义。

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    2019-12-09 xjy02
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    2019-09-01 xjy02
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    2019-12-22 clmlylxy
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    2019-05-26 膀胱癌
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    2019-04-01 yahu
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    2019-04-01 zhouqu_8
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