细胞核DNA感知蛋白质通路在扩大心肌病的人类心脏中被激活
Leila Rouhi1, Sirisha M Cheedipudi1, Benjamin Cathcart1
1Center for Cardiovascular Genetics, Institute of Molecular Medicine, The University of Texas Health Science Center. Houston TX 77030, USA.
概括
这项研究表明,扩大心肌病 (DCM) 的人类心脏中细胞质DNA感知蛋白 (CDSP) 途径的激活增加. 这些发现表明,双链DNA断裂 (DSB) 有助于DCM的发病.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 由双链DNA断裂 (DSB) 引起的基因组不稳定性是一种细胞应激反应.
- 细胞质DNA感知蛋白 (CDSP) 途径,由细胞质DSBs激活,促进炎症.
- 关于在人类扩张性心肌病 (DCM) 中CDSP通路激活的数据有限.
研究的目的:
- 研究人类DCM心脏中关键CDSP路径组件的表达.
- 探索DSB和DCM病原体之间的联系.
主要方法:
- 彗星测定 (单细胞凝电泳) 检测DNA链断裂.
- 免疫血栓检测用于量化CDSP和NFκB通路组件的蛋白质水平.
- RNA-Seq用于测量炎症基因的转录水平.
主要成果:
- 在DCM心脏中,DNA损伤 (COMET细胞) 增加了约2倍.
- 在DCM心脏中观察到高水平的cGAS,TBK1,RELB,P52和P50.
- 检测到超过二十多个炎症基因的转录水平增加.
结论:
- 这项研究提供了第一个证据,证明了人类DCM中CDSP通路的激活.
- 激活的CDSP和DNA损伤响应 (DDR) 途径涉及到DCM开发中的DSB.
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