不确定潜力的克隆性血液形成与急性损伤有关
Caitlyn Vlasschaert1, Cassianne Robinson-Cohen2, Bryan Kestenbaum3
1Department of Medicine, Queen's University, Kingston, Ontario, Canada.
medRxiv : the preprint server for health sciences
|June 9, 2023
概括
不确定潜力的克隆性血液形成 (CHIP) 增加了急性损伤 (AKI) 的风险,并阻碍了的恢复. 这种遗传机制涉及炎症失调,特别是在非DNMT3A CHIP中.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 血液学 血液学 血液学
- 遗传学 遗传学是一种遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 年龄是急性损伤 (AKI) 的首要危险因素,但潜在的生物机制在很大程度上是未知的.
- 不确定潜力的克隆性血液形成 (CHIP),一种涉及骨髓癌驱动基因突变的疾病,与慢性衰老疾病有关.
- 到目前为止,还没有确定AKI风险的确立遗传机制.
研究的目的:
- 调查CHIP是否会增加患急性损伤 (AKI) 的风险.
- 为了确定CHIP是否会影响AKI的恢复.
- 阐明CHIP在AKI病变发生过程中的机械作用.
主要方法:
- 在三大基于人口的队列中评估了CHIP和事件AKI之间的关联 (N=442,153).
- 在ASSESS-AKI队列中评估了CHIP与AKI恢复的关联.
- 使用小鼠模型 (缺血-再输血损伤和单边尿路阻塞) 来检查Tet2-CHIP在AKI中的作用.
主要成果:
- CHIP与AKI (HR 1.26) 和需要透析的AKI (HR 1.65) 的更高风险显著相关.
- 非DNMT3A CHIP与增加的AKI风险 (HR 1.49) 和不解决的AKI模式 (HR 2.3) 有着强烈的关联.
- Tet2-CHIP小鼠表现出更严重的AKI,更大的纤维化,增加了巨细胞的透,以及巨细胞的炎症反应.
结论:
- 这项研究确立了CHIP作为一种导致AKI风险的遗传机制.
- CHIP,特别是非DNMT3A变种,会在AKI后损害功能恢复.
- 在CHIP衍生的巨中异常的炎症反应在AKI的发病和恢复中起着至关重要的作用.
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