Yuqing Miao, Shang Gao, Qing Gao, Jiyang Wang, Ruihao Li, Zuoguan Chen, Yongpeng Diao, Zhiyuan Wu, Yongjun Li
Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Genet. 2022 Nov 16;13:1036233. doi: 10.3389/fgene.2022.1036233. eCollection 2022.
Takayasu arteritis (TA) is a chronic granulomatous vasculitis involving in the main branches of aorta. Previous studies mainly used peripheral blood and some vascular tissues but seldom studies have sequenced vascular tissues. Here in this study, we aimed to explore the alterations of mRNA in TA by performing bulk RNA sequencing. A total of 14 abdominal aortic tissues including 8 from renal transplantation and 6 from patient with TA undergoing bypass surgeries. Bulk RNA sequencing were performed and after the quality control, a total of 1897 transcripts were observed to be significantly differently ( < 0.05 and LogFC > 1) expressed between the TA and control group, among which 1,361 transcripts were in TA group and 536 in the Control group. Reactome Pathway Enrichment Comparison analysis revealed interleukin-10 signaling and signaling by interleukins were highly expressed in TA group. Besides, extracellular matrix organization was also observed in this group. WGCNA and PPI obtained 26 core genes which were highly correlated with the clinical phenotype. We then also perform deconvolution of the bulk RNA-seq data by using the scRNA-seq dataset and noticed the high proportion of smooth muscle cells in our dataset. Additionally, immunohistochemical staining confirmed our bioinformatic analysis that TA aortic tissues express high levels of IL-1R1 and IL-1R2. Briefly, this study revealed critical roles of interleukins in TA pathogenesis, and SMCs may also participate in the reconstruction in vessel wall at late stage of TA.
大动脉炎(TA)是一种累及主动脉主要分支的慢性肉芽肿性血管炎。以往的研究主要使用外周血和一些血管组织,但很少有研究对血管组织进行测序。在本研究中,我们旨在通过进行批量RNA测序来探索TA中mRNA的变化。共收集了14份腹主动脉组织,其中8份来自肾移植患者,6份来自接受搭桥手术的TA患者。进行了批量RNA测序,经过质量控制后,观察到TA组和对照组之间共有1897个转录本表达存在显著差异(<0.05且LogFC>1),其中TA组有1361个转录本,对照组有536个转录本。Reactome通路富集比较分析显示,TA组中白细胞介素-10信号通路和白细胞介素信号通路高度表达。此外,该组还观察到细胞外基质组织化。加权基因共表达网络分析(WGCNA)和蛋白质-蛋白质相互作用(PPI)分析获得了26个与临床表型高度相关的核心基因。然后,我们还使用单细胞RNA测序(scRNA-seq)数据集对批量RNA-seq数据进行反卷积分析,发现我们的数据集中平滑肌细胞比例很高。此外,免疫组织化学染色证实了我们的生物信息学分析结果,即TA主动脉组织中白细胞介素-1受体1(IL-1R1)和白细胞介素-1受体2(IL-1R2)表达水平较高。简而言之,本研究揭示了白细胞介素在TA发病机制中的关键作用,并且平滑肌细胞可能也参与了TA后期血管壁的重建。