Xu Yanan, Li Zihao, Lu Shounan, Wang Chaoqun, Ke Shanjia, Li Xinglong, Yin Bing, Yu Hongjun, Zhou Menghua, Pan Shangha, Jiang Hongchi, Ma Yong
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Hepatic Minimal Invasive Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
J Inflamm Res. 2021 Sep 8;14:4519-4536. doi: 10.2147/JIR.S327467. eCollection 2021.
Itaconate is well known for its strong anti-inflammatory and antioxidant effect, but little is known about the potential role of long non-coding RNAs (lncRNAs) in the underlying mechanisms of hepatic ischemia-reperfusion (IR) injury. The aim of our study is to identify lncRNAs related to IR injury and itaconate-mediated protection and to demonstrate the mechanism by which itaconate acts in liver IR injury from the new perspective of lncRNAs.
4-Octyl itaconate (OI), a membrane-permeable derivative of itaconate, was used as a substitute for itaconate in our study. By using a mouse model of hepatic IR injury, serum and liver samples were collected to measure indexes of liver injury. Then, the liver samples of the mice were subjected to RNA sequencing (RNA-seq) and subsequent bioinformatics analysis.
Itaconate attenuated liver IR injury. A total of 138 lncRNAs and 156 messenger RNAs (mRNAs) were markedly differentially expressed in the IR-damaged liver tissues pretreated with OI compared with the matched liver tissues treated with vehicle. Functional analysis indicated that lncRNAs may indirectly participate in the effects of itaconate. Furthermore, 41 mRNAs were examined for the protein-protein interaction (PPI) network analysis, and a key gene cluster was defined. Then, combined the coexpression analysis and the and regulatory function prediction of lncRNAs, some "candidate" lncRNA-mRNA pairs which might relate to itaconate-mediated liver protection were identified, while the relationship requires future validation.
Our study revealed that itaconate could protect the liver against IR injury and that lncRNAs might play a role in this process. Our study provides a novel way to investigate the mechanism by which itaconate affects hepatic IR injury and exerts its anti-inflammatory and antioxidative stress effects.
衣康酸以其强大的抗炎和抗氧化作用而闻名，但关于长链非编码RNA（lncRNA）在肝缺血再灌注（IR）损伤潜在机制中的作用知之甚少。我们研究的目的是鉴定与IR损伤和衣康酸介导的保护相关的lncRNA，并从lncRNA的新角度阐明衣康酸在肝IR损伤中发挥作用的机制。
在我们的研究中，衣康酸的膜渗透性衍生物4-辛基衣康酸（OI）被用作衣康酸的替代品。通过使用肝IR损伤小鼠模型，收集血清和肝脏样本以测量肝损伤指标。然后，对小鼠的肝脏样本进行RNA测序（RNA-seq）及后续生物信息学分析。
衣康酸减轻了肝IR损伤。与用载体处理的匹配肝脏组织相比，在经OI预处理的IR损伤肝脏组织中，共有138个lncRNA和156个信使RNA（mRNA）明显差异表达。功能分析表明lncRNA可能间接参与衣康酸的作用。此外，对41个mRNA进行了蛋白质-蛋白质相互作用（PPI）网络分析，并定义了一个关键基因簇。然后，结合lncRNA的共表达分析及其调控功能预测，鉴定了一些可能与衣康酸介导的肝脏保护相关的“候选”lncRNA-mRNA对，但其关系尚需未来验证。
我们的研究表明衣康酸可以保护肝脏免受IR损伤，并且lncRNA可能在此过程中发挥作用。我们的研究为研究衣康酸影响肝IR损伤并发挥其抗炎和抗氧化应激作用的机制提供了一种新方法。
