钙粘素相关家族成员3(CDHR3)与lncRNA相互作用参与高血压发病的机制

Cadherin related family member 3 (CDHR3) is a member of cell adhesion molecules, tissue specifically and closely related with inflammation and hypertension. This gene highly expressed in lung tissue, causes increased risk of wheezing illnesses and hospitalizations for childhood asthma through the binding of virus and receptors. Our work showed that CDHR3 gene was found to be expressed in the kidney of SHR hypertensive rats but not in normal rat, however, the role of CDHR3 gene in hypertension pathogenesis is unclear. Increased levels of blood pressure and pro-inflammatory factors, as well as decreased redox ability were noticed in the kidney of specific cdhr3 overexpression mouse generated in our lab. Therefore, we propose that CDHR3 may be related with renal inflammation induction as well as water and salt regulation, finally lead to a blood pressure increase. At the same time, a novel lncRNA-AK125261 was found to be reduced in the plasma of hypertension patients from a case-control study. This lncRNA was illustrated to overlap with CDHR3 gene through a bioinformatics analysis. So, the aim of this project was to investigate the role of CDHR3 gene in the pathogenesis of hypertension, as well as the role of AK125261 towards the regulation of CDHR3 gene. We hope this project could clarify a molecular mechanism associated with hypertension, and provide a new view for the target discovery and treatment for the hypertension disease.

钙粘素相关家族成员3（CDHR3）是细胞黏附分子的一个大类，具有组织特异性，与炎症反应和高血压关系密切。此基因在肺组织高表达，通过增强病毒与受体的结合使儿童哮喘易感增加及呼吸加重。我们的工作发现，CDHR3在SHR高血压大鼠的肾脏中高表达，在正常大鼠肾脏中几乎不表达；然而此基因在高血压发病过程中的机制并不清楚。我们已构建的肾脏特异性CDHR 3过表达小鼠血压升高、促炎性因子增加、氧化还原能力降低。因此，我们提出假说，CDHR3可能通过诱导肾脏炎症，调节水盐代谢，从而导致血压的升高。同时，我们在高血压人群队列研究中发现了一条高血压患者表达显著下调的lncRNA-AK125261，其与CDHR3部分重叠，可能参与CDHR3的表达调控。本项目旨在研究CDHR3基因在高血压发病过程中的作用以及AK125261如何参与CDHR3调节，希望可以阐明一个与高血压发病相关的新基因及调控的机制。

高血压是最常见的心血管疾病之一，也是众多心血管疾病如冠心病、心力衰竭等疾病的危险因素。随着我国人口的老龄化和人们生活水平方式的改变，高血压的患病率正逐渐升高。90-95%的高血压患者属于原发性高血压，此种血压增高病因学不明，可能与基因异质性、多因素病因有关. 近年来，越来越多的证据表明，非编码RNA在转录后水平调控基因，在高血压的发病过程中起着重要的作用。非编码RNA包括小RNA（miRNA）、长链非编码RNA（lncRNA）、 环状RNA（circRNA）。本项目旨在研究通过人群队列发现的高血压病人血浆中低表达的lncRNA-AK125261对CDHR3基因的调节，及其诱导肾脏炎症、调节水盐代谢，从而引起血压的升高的潜在作用；同时，检测高血压疾病状态时，外周循环的动脉血和静脉血中的miRNA，从差异表达、富集靶基因及其调控转录因子与心血管疾病之间的潜在的功能关联角度，提出有必要重新评估某些静脉miRNA的有效性。以上结果阐明，非编码RNA可以作为高血压发病的靶点发现和疾病治疗提供一种新的可能性。