Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Department of Pathology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Int J Biol Sci. 2020 Feb 10;16(7):1166-1179. doi: 10.7150/ijbs.41293. eCollection 2020.
Carbon tetrachloride (CCl4), Concanavalin A (ConA), bile duct ligation (BDL), and liver resection (LR) are four types of commonly used mouse models of acute liver injury. However, these four models belong to different types of liver cell damage while their application situations are often confounded. In addition, the systematic changes of multiple extra-liver organs after acute liver injury and the crosstalk between liver and extra-liver organs remain unclear. Here, we aim to map the morphological, metabolomic and transcriptomic changes systematically after acute liver injury and search for the potential crosstalk between the liver and the extra-liver organs. Significant changes of transcriptome were observed in multiple extra-liver organs after different types of acute liver injury despite dramatic morphological damage only occurred in lung tissues of the ConA/BDL models and spleen tissues in the ConA model. Liver transcriptomic changes initiated the serum metabolomic alterations which correlated to transcriptomic variation in lung, kidney, and brain tissues of BDL and LR models. The potential crosstalk might lead to pulmonary damage and development of hepatorenal syndrome (HRS) and hepatic encephalopathy (HE) during liver injury. Serum derived from acute liver injury mice damaged alveolar epithelial cells and human podocytes . Our data indicated that different types of acute liver injury led to different transcriptomic changes within extra-liver organs. Integration of serum metabolomics and transcriptomics from multiple tissues can improve our understanding of acute liver injury and its effect on the other organs.
四氯化碳（CCl4）、刀豆球蛋白 A（ConA）、胆管结扎（BDL）和肝切除（LR）是四种常用的小鼠急性肝损伤模型。然而，这四种模型属于不同类型的肝细胞损伤，但其应用情况往往相互混淆。此外，急性肝损伤后多个肝外器官的系统变化以及肝与肝外器官之间的相互作用仍不清楚。在这里，我们旨在系统地绘制急性肝损伤后形态、代谢组学和转录组学的变化，并寻找肝脏和肝外器官之间的潜在相互作用。尽管 ConA/BDL 模型的肺组织和 ConA 模型的脾组织仅发生明显的形态损伤，但不同类型的急性肝损伤后多个肝外器官的转录组发生了显著变化。肝转录组变化引发了血清代谢组的改变，这与 BDL 和 LR 模型中肺、肾和脑组织的转录组变化相关。潜在的相互作用可能导致肝损伤期间发生肺损伤和肝肾综合征（HRS）和肝性脑病（HE）的发展。来自急性肝损伤小鼠的血清损伤肺泡上皮细胞和人足细胞。我们的数据表明，不同类型的急性肝损伤导致肝外器官内的转录组发生不同的变化。来自多个组织的血清代谢组学和转录组学的整合可以提高我们对急性肝损伤及其对其他器官影响的理解。
