Research Paper Volume 12, Issue 22 pp 23187—23199
Identification and characterization of dynamically regulated hepatitis-related genes in a concanavalin A-induced liver injury model
- 1 Translational Medicine Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
- 2 Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
- 3 Department of Radiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
- 4 Institute of Hepatology and Metabolic Diseases, Hangzhou Normal University, Hangzhou 310015, China
Received: June 17, 2020 Accepted: August 31, 2020 Published: November 18, 2020
https://doi.org/10.18632/aging.104089How to Cite
Copyright: © 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 in vivo 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 Cd63, Saa3, Slc10a1, Nrxn1, Ugt2a3, were verified in vivo. Further, Cluster determinant 63 (Cd63) 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 Cd63 might have utility for the protection of hepatocellular damage.
Abbreviations
AIH: Autoimmune hepatitis; ConA: Concanavalin A; GO: Gene Ontology; KEGG: Kyoto encyclopedia of genes and genomes; Cd63: Cluster determinant 63; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HE: Hematoxylin-eosin; WGCNA: Weighted correlation network analysis; Mmp3: Matrix Metallopeptidase 3; Aadac: Arylacetamide deacetylase; Timp1: Tissue inhibitor of metalloproteinases-1; Saa: Serum amyloid A.