Tian Xinyao, Hu Yan, Liu Yuanxing, Yang Zhe, Xie Haiyang, Zhou Lin, Zheng Shusen
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Combined Multi-organ Transplantation, National Health Commission of PRC, Hangzhou, China.
Front Med (Lausanne). 2021 Mar 8;8:626948. doi: 10.3389/fmed.2021.626948. eCollection 2021.
Ischemic preconditioning (IPC) represents an effective intervention to relieve hepatic ischemia-reperfusion injury (IRI). Systematic detection of circRNA expression revealing the protection effect of IPC still remains to be elucidated. Here, we applied a microarray to detect circRNA and mRNA expression in ischemic liver with and without IPC ( = 3 in each group). Compared with the sham group, there were 39 circRNAs and 432 mRNAs increased and 38 circRNAs and 254 mRNAs decreased (fold change ≥1.5, < 0.05) in the group of hepatic IRI. As the result of IPC intervention, 43 circRNAs and 64 mRNAs were increased, and 7 circRNAs and 31 mRNAs were decreased in the IPC group when compared with IRI. We then identified circRNA_017753 as the most possible target that may closely relate to IPC protective signaling and predicted Jade1 as the target related to circRNA_017753. Three possible circRNA-miRNA-mRNA axes were constructed that may play a vital role in protective mechanisms in IPC. The study for the first time systematically detects the dysregulated circRNAs and mRNAs in response to hepatic IRI and IPC intervention. Our profile and bioinformatic analysis provide numerous novel clues to understanding the pathophysiologic mechanism of IPC protection against hepatic IRI.
缺血预处理(IPC)是一种缓解肝脏缺血再灌注损伤(IRI)的有效干预措施。通过系统检测circRNA表达来揭示IPC的保护作用仍有待阐明。在此,我们应用微阵列检测有或无IPC的缺血肝脏中circRNA和mRNA的表达(每组n = 3)。与假手术组相比,肝IRI组中有39种circRNA和432种mRNA表达上调,38种circRNA和254种mRNA表达下调( fold change≥1.5,P < 0.05)。作为IPC干预的结果,与IRI组相比,IPC组中有43种circRNA和64种mRNA表达上调,7种circRNA和31种mRNA表达下调。然后,我们确定circRNA_017753是最可能与IPC保护信号密切相关的靶点,并预测Jade1是与circRNA_017753相关的靶点。构建了三个可能在IPC保护机制中起关键作用的circRNA-miRNA-mRNA轴。本研究首次系统检测了肝脏IRI和IPC干预后失调的circRNA和mRNA。我们的图谱和生物信息学分析为理解IPC对肝脏IRI保护的病理生理机制提供了许多新线索。