Dataset Information

Circular RNAs associated with a mouse model of concanavalin A-induced autoimmune hepatitis: Preliminary screening and comprehensive functional analysis.

ABSTRACT: Without treatment, autoimmune hepatitis (AIH) often leads to cirrhosis, liver failure, and in some cases, death. However, the pathogenesis of AIH remains incompletely understood. Here, we explored the relationship between differentially expressed circRNAs (DECs) and development of AIH by obtaining an expression profile of DECs in concanavalin A-induced AIH mouse model by microarray. In total, we identified 27 DECs; the host genes of these DECs were annotated with 140 GO terms and 19 pathways, revealing potential roles in the metabolism of cellular ions and regulation of protein expression, as well as possible involvement in endocytosis and apoptosis. We constructed a circRNA-miRNA network which was used to infer that a mmu_circ_0001520/mmu-miR-193b-3p/MAPK10 network may be associated with the occurrence of AIH. These findings may help lay the foundation for validation of the potential roles of circRNAs in AIH.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7609805 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circular RNAs associated with a mouse model of concanavalin A-induced autoimmune hepatitis: preliminary screening and comprehensive functional analysis.

Liu Yang Y Li Zhencheng Z Hao Jianheng J Chen Hao H Hou Tiezheng T Hao Huiqin H

FEBS open bio 20201014 11

Without treatment, autoimmune hepatitis (AIH) often leads to cirrhosis, liver failure and, in some cases, death. However, the pathogenesis of AIH remains incompletely understood. Here, we explored the relationship between differentially expressed circular RNAs (DECs) and development of AIH by obtaining an expression profile of DECs in a concanavalin A-induced AIH mouse model by microarray. In total, we identified 27 DECs; the host genes of these DECs were annotated with 140 Gene Ontology terms a ...[more]

PMID: 32965791

Similar Datasets

Project description:Autoimmune hepatitis (AIH) is a progressive inflammation-associated liver injury. Pyroptosis is a novel inflammatory programmed cell death wherein gasdermin D (GSDMD) serves as the executioner. Our work challenged Gsdmd-/- mice with concanavalin A (ConA) to try to unveil the actual role of GSDMD in AIH. After ConA injection, Gsdmd-/- mice exhibited more severe liver damage characterized by a lower survival rate, more extensive hepatocyte necrosis and apoptosis, and higher serum transaminase levels, indicating the protection of GSDMD in ConA-induced AIH. Furthermore, the Gsdmd-/- mice exhibited higher hepatic expression and serum levels of inflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-17A [IL-17A]) and more infiltration of macrophages and neutrophils after ConA treatment than did wild-type (WT) mice. Gsdmd-/- mice with AIH showed increased hepatic l-glutamine levels but decreased glycerophospholipid metabolites levels. L-glutamine levels showed positive correlations while glycerophospholipid metabolites showed negative associations with liver injury indexes and inflammation markers. We further observed a destroyed intestinal barrier in Gsdmd-/- mice after ConA injection as indicated by decreased transcriptional expressions of Tjp1, Ocln, Reg3g, and Muc2. ConA-treated Gsdmd-/- mice also exhibited higher serum LPS binding protein (LBP) concentrations and hepatic Tlr4 and Cd14 mRNA levels. Further fecal 16S rRNA gene sequencing demonstrated decreased relative abundances of Lactobacillus and Roseburia but increased relative abundances of Allobaculum and Dubosiella in Gsdmd-/- mice with AIH. Lactobacillus was negatively correlated with liver injury and inflammation indexes and positively associated with Ocln, Muc2, and Reg3g levels. Allobaculum was positively related to liver injury and inflammatory cytokines and negatively correlated with gut barrier indexes. IMPORTANCE Our study provides the first direct clues to the protective role of gasdermin D (GSDMD) in autoimmune hepatitis (AIH). We demonstrated that Gsdmd knockout exacerbated concanavalin A (ConA)-induced AIH in mice. It may be due to the destroyed intestinal barrier and changes in certain intestinal microbes and hepatic metabolites resulting in increased liver injury and inflammation in ConA-treated Gsdmd-/- mice. This finding suggested a nonnegligible role of GSDMD in AIH and also confirmed its physiological nonpyroptosis effects on the host. The role of GSDMD in autoimmune liver diseases or other liver diseases is complex and intriguing, deserving deep investigation.

Dataset Information

Circular RNAs associated with a mouse model of concanavalin A-induced autoimmune hepatitis: Preliminary screening and comprehensive functional analysis.

Publications

Circular RNAs associated with a mouse model of concanavalin A-induced autoimmune hepatitis: preliminary screening and comprehensive functional analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets