在肺动脉高血压中LncRNA-536和RNA结合蛋白RBM25的相互作用
Aatish Mahajan1, Ashok Kumar1, Ling Chen1
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS.
bioRxiv : the preprint server for biology
|September 10, 2024
概括
长非编码RNA ENST00000495536 (lnc-536) 通过降低HOXB13.的调节来驱动肺动脉高血压. 在体内抑制Inc-536可降低肺高血压和血管重塑,提供潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
- 在RNA生物学,RNA生物学.
背景情况:
- 肺动脉高血压 (PAH) 涉及肺动脉光滑肌肉细胞 (PASMC) 的高增殖.
- 了解驱动PASMC增生症的分子机制对于PAH治疗至关重要.
研究的目的:
- 阐明长非编码RNA ENST00000495536 (lnc-536) 与PASMC增生症中抗增殖因子HOXB13之间的机制联系.
- 研究INC-536在肺高血压发展中的作用.
主要方法:
- 利用反感性寡核酸 (GapmeRs) 和等离子体过度表达来操纵PDGF治疗和异常性PAH (IPAH) PASMC中的Inc-536水平.
- 进行了 lnc-536 下拉测试,以确定相互作用的蛋白质,包括RNA结合蛋白RBM25和转录调节器SFPQ.
- 在Sugen-hypoxia和HIV-转基因的肺高血压大鼠模型中评估了Inc-536 Knockdown在体内疗效.
主要成果:
- 在PASMC中增加的Inc-536水平与增加的增殖和降低HOXB13表达相关.
- lnc-536 knockdown 在体内改善了肺高血压,逆转了RVSP和富尔顿指数的增加,并减少了肺血管重塑.
- lnc-536与RBM25相互作用,隔离SFPQ,从而降低HOXB13的调节,从而促进PASMC的扩散.
结论:
- lnc-536作为RBM25的分子诱,导致SFPQ封存.
- 这种机制导致HOXB13的表达减少,导致光滑肌肉细胞的过度增殖,并导致PAH的发病.
- lnc-536/HOXB13轴代表了肺动脉高血压的潜在治疗标.
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