鉴定和描述在刀豆球蛋白 A 诱导的肝损伤模型中动态调控的肝炎相关基因。
Identification and characterization of dynamically regulated hepatitis-related genes in a concanavalin A-induced liver injury model.
机构信息
Translational Medicine Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China.
Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
出版信息
Aging (Albany NY). 2020 Nov 18;12(22):23187-23199. doi: 10.18632/aging.104089.
BACKGROUND
Concanavalin A (ConA)-induced liver damage of mice is a well-established murine model mimicking the human autoimmune hepatitis (AIH). However, the pathogenic genes of the liver injury remain to be revealed.
METHODS
Using time-series liver transcriptome, top dynamic genes were inferred from a set of segmented regression models, and cross-checked by weighted correlation network analysis (WGCNA). AIH murine models created by ConA were used to verify the effect of these genes.
RESULTS
We identified 115 top dynamic genes, of which most were overlapped with the hub genes determined by WGCNA. The expression of several top dynamic genes including were verified . Further, Cluster determinant 63 () knockdown in mice treated with ConA showed significantly less liver pathology and inflammation as well as higher survival rates than the corresponding controls.
CONCLUSION
We have identified the top dynamic genes related to the process of acute liver injury, and highlighted a targeted strategy for might have utility for the protection of hepatocellular damage.
背景
刀豆球蛋白 A（ConA）诱导的小鼠肝损伤是一种模拟人类自身免疫性肝炎（AIH）的成熟的小鼠模型。然而，导致肝损伤的致病基因仍有待揭示。
方法
使用时间序列肝转录组，从一组分段回归模型推断出顶级动态基因，并通过加权相关网络分析（WGCNA）进行交叉检查。使用 ConA 诱导的 AIH 小鼠模型来验证这些基因的作用。
结果
我们鉴定出 115 个顶级动态基因，其中大多数与 WGCNA 确定的枢纽基因重叠。包括 在内的几个顶级动态基因的表达得到了验证。进一步的，Cluster determinant 63 () 在 ConA 处理的小鼠中的敲低显示出明显较少的肝病理学和炎症以及更高的存活率，比相应的对照组要好。
结论
我们已经确定了与急性肝损伤过程相关的顶级动态基因，并强调了针对 的靶向策略可能对保护肝细胞损伤具有实用价值。
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