长非编码RNA的消去 Hoxb3os 在小鼠中恶化细胞生成 多囊性脏疾病
Ivan Weisser1, Kara Eckberg1, Stephen D'Amico2
1Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Journal of the American Society of Nephrology : JASN
|November 13, 2023
概括
这项研究表明,长非编码RNAHoxb3os在自身主导多性脏病 (ADPKD) 中被下调. 它的缺失会通过激活mTORC2信号来恶化囊的生长,这表明lncRNAs是PKD的潜在治疗点.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 自体主导多囊性病 (ADPKD) 是一种导致囊的遗传疾病,主要是由于PKD1或PKD2的突变.
- 长非编码RNAs (lncRNAs) 越来越多地被认可为它们在疾病中的作用,但它们在ADPKD中的参与仍然在很大程度上未被探索.
研究的目的:
- 研究lncRNA Hoxb3os在ADPKD.病原发生中的作用.
- 为了确定Hoxb3os是否会影响类哺乳动物的拉巴素 (mTOR) /Akt信号通路在病的背景下.
主要方法:
- 在多囊病 (PKD) 的小鼠模型中,Hoxb3os表达的消去.
- 对mTOR/Akt信号通路组件的分析,包括Rictor和酸化Akt.
- 对转基因小鼠细胞增殖和囊发育的评估.
主要成果:
- 霍克斯b3os-null小鼠表现出激活的mTOR/Akt信号传递和增加的细胞增殖.
- 切除Hoxb3os显著加剧了两个不同的Pkd1小鼠模型中的囊生长和数量.
- 双击的小鼠 (Pkd1和Hoxb3os) 显示了增强的mTORC2信号,由增加的Rictor和酸化Akt水平表明.
结论:
- 在ADPKD中对Hoxb3os的下调有助于通过调节mTORC2信号的失调导致囊发生.
- 针对像Hoxb3os这样的lncRNAs,为PKD提供了一个潜在的治疗策略.
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