NFAT5基因的研究意义
摘要:活化T细胞核因子是一类具有多向调节功能的转录因子。在免疫应答中诱导基因转录,促进T细胞活化。NAFT家族有5个成员,分别为NFAT1(NFATc2/NFATp),NFAT2(NFATc1/NFATc),NFAT3(NFATc4),NFAT4(NFATc3/NFATx)和NFAT5。NFAT5因高渗透压而活化,而NFAT1-4受Ca2 /钙调神经磷酸酶(CaN)信号通路调节。NFAT3 是该家族中唯一在免疫细胞中无表达者, NFAT5是该家族中唯一不受钙信号调控者。NFAT5是截止目前唯一已知的一种哺乳动物细胞渗透压反应调节因子,已有许多研究结果表明,NFAT5在细胞应答高渗应激中起关键作用。此外,NFAT5还在代谢调节、DNA损伤修复、免疫调节等多种生命活动中发挥作用。NFAT5可以帮助维持巨噬细胞抗病原体功能的稳健性;可以独立于其渗透反应活性调节巨噬细胞功能以及调节巨噬细胞对病原体衍生产物的反应,除此之外,NFAT5还具有调节胸腺细胞个体发育以及成熟T淋巴细胞的功能。然而,爬行动物中NFAT5的功能目前尚不清楚我们实验目的构建NFAT5表达质粒并探究其功能,初步探讨其在爬行动物免疫系统中的作用。
关键词:活化T细胞核因子;NFAT5;免疫系统;巨噬细胞;T淋巴细胞;
Research significance of NFAT5 gene
Abstract: Nuclear factor of activated T cells is a class of transcription factors with pleiotropic regulatory functions. They induce gene transcription in the immune response and promote T cell activation. there are five members of the NAFT family, NFAT1 (NFATc2/NFATp), NFAT2 (NFATc1/NFATc), NFAT3 (NFATc4),NFAT4 (NFATc3/NFATx), and NFAT5. NFAT5 is activated by high osmotic pressure, and NFAT3 is the only member of this family that is not expressed in immune cells, and NFAT5 is the only member of this family that is not regulated by calcium signaling. NFAT5 is the only mammalian cellular osmolarity regulator known to date, and many studies have shown that NFAT5 plays a key role in cellular response to hyperosmotic stress. In addition, NFAT5 plays a role in metabolic regulation, DNA damage repair, immune regulation and many other life activities. NFAT5 can help maintain the robustness of macrophage function against pathogens, regulate macrophage function independently of its osmotic response activity and regulate macrophage responses to pathogen-derived products. and mature T lymphocytes.However, the function of NFAT5 in reptiles is still unclear. Our experiments aimed to construct NFAT5 expression plasmids and explore its function, and initially explore its role in the reptile immune system。
Keywords: nuclear factor of activated T cells; NFAT5; immune system; macrophages; T lymphocytes.
1.活化T细胞核因子
1.1活化T细胞核因子家族
活化T细胞核因子(Nuclear factor of activated T cell,NFAT)是一类具有多向调节功能的转录激活因子,是炎症增强体的重要组成部分,最初作为与人T细胞中白介素-2(IL-2)启动子的抗原受体应答元件-2(ARRE-2)相结合的诱导型核因子,在活化T细胞的核提取物中被发现,具有转录活性,是一类具有多向调节功能的转录因子。在免疫应答中诱导基因转录,促进T细胞活化。随后的一系列研究表明,NFAT除了在在T细胞中表达外,还普遍表达于哺乳动物的各种免疫与非免疫细胞中,在细胞周期、胚胎发育以及器官发生(特别是心脏、造血、骨骼和神经元系统)中起到多重调节作用[5]。近年来研究显示NFAT家族在调控肿瘤细胞生长、转移和血管生成等恶性生物学过程中也发挥重要的作用[4]。
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