Nat.Med:HIPK2激酶——肾脏疾病药物新靶标

2012-04-10 范振光 生物谷

    2012年3月12日,据《每日科学》,来自西奈山医学院的研究人员,鉴定出了在肾间质纤维化(一种能导致肾功能衰竭的疾病)中扮演着重要角色的一种调控蛋白。该调控蛋白的发现,为这种影响着数以百万计美国人的肾脏疾病的治疗,提供了一个全新的治疗靶标。研究结果发表于3月11日的《自然医学》(Nat Med. 2012 Mar 11.)。      

HIPK2激酶 调控蛋白 肾间质纤维化     2012年3月12日,据《每日科学》,来自西奈山医学院的研究人员,鉴定出了在肾间质纤维化(一种能导致肾功能衰竭的疾病)中扮演着重要角色的一种调控蛋白。该调控蛋白的发现,为这种影响着数以百万计美国人的肾脏疾病的治疗,提供了一个全新的治疗靶标。研究结果发表于3月11日的《自然医学》(Nat Med. 2012 Mar 11.)。       该项研究由肾脏病学、药理学及系统药物治疗教授John Cijiang He博士及西奈山医学院药理学及系统治疗助理教授Avi Ma ayan博士领导。研究小组研究了3种小鼠纤维化模型:第一组小鼠其基因组中纳入了HIV病毒蛋白基因,第二组小鼠注射了高剂量的叶酸,第三组小鼠中单侧肾脏的肾脏过滤被封阻。所有这些因素都能导致肾间质纤维化。       研究人员收集了小鼠的遗传物质,并与那些无肾脏纤维化小鼠的遗传物质进行了比较。通过应用一种被称为Expression2Kinases(由西奈山Ma ayan实验室开发)的新计算系统生物学方法及软件,对这些实验结果进行了比较。他们发现,一种被称为HIPK2的蛋白激酶(或称调节子),在肾间质纤维化小鼠中高度活跃。HIPK2调控着特定基因的表达方式,当HIPK2高度活跃时,便导致了肾间质纤维化。He博士和Ma ayan博士也发现,当消除HIPK2后,肾间质纤维化情况就不是那么太明显,同时小鼠的病症得到了极大地改善。       "我们的发现对那些患肾脏疾病的人们及我每天所治疗的患者来说,具有非常重要的意义,"He博士说道。"像HIPK2这类蛋白激酶,是非常有效的治疗靶标。我们期待着进一步的探索。"       系统学方法的纳入,使西奈山研究团队能够鉴定出一个药物靶标,这是一个在慢性疾病中被修饰了的调控蛋白。HIPK2在肾间质纤维化中的高活性,单靠检测基因表达变化的标准方法是检测不出来的,但通过计算系统生物学来建模蛋白质网络,研究团队能够追踪到这种调控蛋白,HIPK2。现在,西奈山的科学家们有望能够开发出一种干预药物,来抑制HIPK2的活性。       "这项研究是我们在西奈山所正在做的转化研究中的一个重要例子,"Ma ayan博士说道。"通过使用演算法及所开发的软件,我们与He博士更好地了解了导致肾脏纤维化的因素,我们现在离寻找一种治疗策略以解决这一影响数百万之众美国人的疾病,又近了一步。"       这项研究由国立卫生研究院(NIH)下属的国家糖尿病、消化道及肾脏疾病研究所(the National Institute of Diabetes and Digestive and Kidney Diseases)资助。

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    2012-05-13 liye789132251
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    2012-04-12 zhaojie88
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    2012-04-12 redcrab
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