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活性蛋白和微管网调节器WHAMM被确定为关键病风险基因
Dhanunjay Mukhi1, Lakshmi Prasanna Kolligundla1, Tomohito Doke2
1Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Philadelphia, PA, USA.
Cell reports
|March 26, 2025
概括
与病相关的遗传变异调节了WHAMM,这是一种对细胞死亡至关重要的蛋白质. 减少WHAMM或抑制actin动力学可以在小鼠模型中防止损伤.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 脏疾病影响全球数以百万计的人,超过800个遗传位置与功能障碍有关.
- 导致功能障碍的特定基因,细胞类型和机制在很大程度上是未知的.
研究的目的:
- 确定导致病的新型遗传因素和机制.
- 调查与,膜和微管 (WHAMM) 相关的黄蜂同类在功能障碍中的作用.
主要方法:
- 全基因组关联研究以确定与功能障碍相关的遗传变异.
- 在小鼠模型和人类病患者中分析WHAMM表达.
- 研究WHAMM删除对小鼠各种侮辱引起的损伤的影响.
- 在体外研究以阐明WHAMM在细胞死亡途径中的作用,包括线粒体细胞染色体c释放和ASC斑块形成.
- 在实验性病模型中评估抑制actin动态的治疗潜力.
主要成果:
- 15号染色体上的核酸变异与功能障碍有关,并调节WHAMM表达.
- 在患有急性和慢性病的小鼠和人类患者中,WHAMM表达升高.
- 缺少WHAMM的小鼠在暴露于毒药物 (cisplatin,叶酸) 和单边尿路阻塞后,表现出减少的损伤.
- WHAMM通过调节由线粒体和ASC斑形成的actin依赖的cytochromec释放来影响细胞死亡.
- 在实验环境中,对actin动态的药理抑制证明了对脏疾病的保护作用.
结论:
- WHAMM被确定为脏疾病发展的关键调节者.
- 针对WHAMM或actin动态呈现出病的潜在治疗策略.
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