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非编码RNA参与狼疮等自身免疫病的病理机制及临床意义
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信号通路中的一些关键分子的表达或功能失调会导致细胞内信号通路紊乱从而参与疾病。非编码RNA(ncRNA),包括miRNA和长链非编码RNA(lncRNA)在信号传递通路的调节中有着重要作用。我们以系统性红斑狼疮这一重要自身免疫疾病为研究模型来研究非编码RNA在自身免疫病关键致病通路中的作用。我们已发表的系列工作揭示了遗传及表观遗传因子可导致与狼疮重要免疫表型相关的一组miRNA表达异常。我们也进一步多方位阐述了多个miRNA分别或协同参与狼疮脏器受累相关的免疫炎症通路的异常活化的分子机制。更为重要的是,通过体外实验和体内研究证实了靶向干预疾病相关miRNA可以改变疾病的异常免疫病理表型(Nat Med 2012; PLoS Genet 2011; Blood 2010;J Immunol 2010; Arthritis Rheum 2009; 2010; 2011。受邀在Nat Rev Rheumatol上发表特邀综述)。干扰素通路异常激活在系统性红斑狼疮的发病中起着重要作用。近期我们的研究发现lncRNA能调节干扰素通路中的一个关键转录因子STAT1的表达从而参与STAT1信号传递通路的调节。这些研究为深入阐明ncRNA在自身免疫性疾病发生发展中的细胞和分子机理,为今后发展ncRNA靶向治疗提供理论基础。
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