IFI6对皮肤细胞的辐射防护作用及机制探究
首发时间:2019-11-28
摘要:皮肤是人体的最大器官。放射性皮肤损伤常由放射治疗、核事故等引起,创面迁延不愈,尚无特效治疗手段。因而,寻找预防和治疗皮肤辐射损伤的有效方法显得极为重要。本研究通过mRNA表达谱芯片检测受照射人皮肤角质细胞HaCaT中差异表达的基因,发现干扰素诱导蛋白6(IFI6)上调变化最显著。IFI6是早期被鉴定的干扰素诱导基因之一。作为Ⅰ型干扰素诱导激活基因家族成员,IFI6参与多种免疫调控通路,相关途径包括干扰素γ信号转导通路和细胞因子信号转导通路,在抗病毒和细胞凋亡调节中具有重要作用,甚至是直接效应产物。但是IFI6在放射性皮肤损伤领域的研究尚未见报导。本研究发现,IFI6在照射后的皮肤细胞内高表达,并且显著增加皮肤细胞的辐射抗性,具体表现为促进照后皮肤细胞的增殖能力,降低辐射诱导的细胞凋亡水平。与此同时,IFI6在照后的皮肤细胞内向细胞核聚集,与另一入核蛋白SSBP1发生相互作用,显著影响内质网应激通路中热休克调节因子1(HSF1)的转录活性。综上所述,IFI6通过调控HSF1介导的内质网应激过程从而抑制辐射诱导的皮肤细胞损伤,降低皮肤细胞的辐射敏感性。
关键词: IFI6 电离辐射 放射性皮肤损伤 细胞凋亡 内质网应激
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Radio-protective role of IFI6 on human skin cells and its mechanism
Abstract:Skin is the largest organ of human body. Radiation-induced skin injury caused by radiotherapy and nuclear accidents often prolonged unhealed, and there is no specific treatment for that. Therefore, it is extremely important to find effective ways to prevent and treat radiation-induced skin lesions. In this study, mRNA expression spectrum chip was used to detect the differentially expressed mRNAs in irradiated skin keratinocytes (HaCaT), and interferon-inducible protein 6 (IFI6) was most up-regulated. IFI6 was first identified as one of the many genes induced by interferon. As a member of type I interferon inducible genes, IFI6 is involved in a variety of immune regulatory pathways, including interferon γ signal transduction pathway and cytokine signal transduction pathway. IFI6 plays an important role in the regulation of apoptosis and antivirus, even act as the direct effects in such processes. However, the study of IFI6 in radiation-induced skin injury has not been reported. In this study, we found that IFI6 is overexpressed in irradiated skin cells so as to significantly increase its radiation resistance through promoting the proliferation capacity and reducing the level of apoptosis of irradiated skin cells. At the same time, IFI6 could translocated into nuclear in irradiated skin cells and interacted with another nuclear translocation protein SSBP1, which significantly affected the transcriptional activity of heat shock regulator 1 (HSF1) in endoplasmic reticulum stress pathway. To sum up, IFI6 overexpression reduces the radiosensitivity of skin cells so as to inhibit radiation-induced skin cell injury by regulating HSF1 mediated endoplasmic reticulum stress.
Keywords: IFI6 Ionizing radiation Radiation-induced skin injury Cell apoptosis Endoplasmic reticulum stress
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IFI6对皮肤细胞的辐射防护作用及机制探究
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