Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model
Abstract Background The prevalence of autoimmune hepatitis (AIH) is increasing, and its early clinical diagnosis is difficult. The pathogenesis of AIH remains unclear, and AIH-related studies are largely limited because of lack of suitable mouse models. Methods To obtain a good tool for research on...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2020-01-01
|
Series: | Journal of Translational Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12967-019-02180-3 |
id |
doaj-95f66c8dd80f4ff686c8c1efc62c4856 |
---|---|
record_format |
Article |
spelling |
doaj-95f66c8dd80f4ff686c8c1efc62c48562021-01-10T12:16:35ZengBMCJournal of Translational Medicine1479-58762020-01-0118111610.1186/s12967-019-02180-3Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse modelHan Wang0Wei Yan1Zuohua Feng2Yuan Gao3Liu Zhang4Xinxia Feng5Dean Tian6Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background The prevalence of autoimmune hepatitis (AIH) is increasing, and its early clinical diagnosis is difficult. The pathogenesis of AIH remains unclear, and AIH-related studies are largely limited because of lack of suitable mouse models. Methods To obtain a good tool for research on AIH, we first established an improved immune-mediated mouse model that can mimic the pathological process of AIH as in the human body, through repeated injections of human cytochrome P450 2D6 (CYP2D6) plasmid. Next, a proteomic analysis based on isobaric tag (IBT) technology was performed to detect the differentially expressed proteins (DEPs), and related biological functions and pathways in the plasma of AIH and normal mice. Finally, we performed enzyme-linked immunosorbent assay (ELISA) to further confirm the most abundant DEP in the plasma of patients with AIH. Results Autoantibodies and the characteristic pathology of AIH were observed in our mouse model. Inflammatory infiltration also increased in the livers of AIH mice over time and plateaued by day 42 post the first injection. Chronic hepatitis was most severe on day 35 with the development of fibrosis as well, and the plasma of AIH mice were collected for proteomic analysis. A total of 176 DEPs were found in this experiment, of which 148 DEPs were up-regulated and 28 DEPs were down-regulated. Thirty significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (P < 0.05) were detected. Arginine biosynthesis was found to be the most significant pathway involved in the AIH process. During the Gene Ontology (GO) analysis, most DEPs were found to be involved in the binding, cellular, and metabolic processes. Using ELISA, the most overexpressed DEP, serum amyloid A 1 (SAA1), was confirmed to be increased specifically in the plasma of patients with AIH compared to other chronic hepatitis. Different plasma levels of SAA1 were also found related to different grades of inflammation and stages of fibrosis in the liver of patients with AIH. Conclusions Our study is the first to describe the proteomics analysis of a true sense of AIH mouse model, which is beneficial for a better understanding of AIH pathogenesis and identifying potential biomarkers for its clinical diagnosis.https://doi.org/10.1186/s12967-019-02180-3Autoimmune hepatitisMouse modelProteomeKEGGSAA1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Han Wang Wei Yan Zuohua Feng Yuan Gao Liu Zhang Xinxia Feng Dean Tian |
spellingShingle |
Han Wang Wei Yan Zuohua Feng Yuan Gao Liu Zhang Xinxia Feng Dean Tian Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model Journal of Translational Medicine Autoimmune hepatitis Mouse model Proteome KEGG SAA1 |
author_facet |
Han Wang Wei Yan Zuohua Feng Yuan Gao Liu Zhang Xinxia Feng Dean Tian |
author_sort |
Han Wang |
title |
Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model |
title_short |
Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model |
title_full |
Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model |
title_fullStr |
Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model |
title_full_unstemmed |
Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model |
title_sort |
plasma proteomic analysis of autoimmune hepatitis in an improved aih mouse model |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2020-01-01 |
description |
Abstract Background The prevalence of autoimmune hepatitis (AIH) is increasing, and its early clinical diagnosis is difficult. The pathogenesis of AIH remains unclear, and AIH-related studies are largely limited because of lack of suitable mouse models. Methods To obtain a good tool for research on AIH, we first established an improved immune-mediated mouse model that can mimic the pathological process of AIH as in the human body, through repeated injections of human cytochrome P450 2D6 (CYP2D6) plasmid. Next, a proteomic analysis based on isobaric tag (IBT) technology was performed to detect the differentially expressed proteins (DEPs), and related biological functions and pathways in the plasma of AIH and normal mice. Finally, we performed enzyme-linked immunosorbent assay (ELISA) to further confirm the most abundant DEP in the plasma of patients with AIH. Results Autoantibodies and the characteristic pathology of AIH were observed in our mouse model. Inflammatory infiltration also increased in the livers of AIH mice over time and plateaued by day 42 post the first injection. Chronic hepatitis was most severe on day 35 with the development of fibrosis as well, and the plasma of AIH mice were collected for proteomic analysis. A total of 176 DEPs were found in this experiment, of which 148 DEPs were up-regulated and 28 DEPs were down-regulated. Thirty significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (P < 0.05) were detected. Arginine biosynthesis was found to be the most significant pathway involved in the AIH process. During the Gene Ontology (GO) analysis, most DEPs were found to be involved in the binding, cellular, and metabolic processes. Using ELISA, the most overexpressed DEP, serum amyloid A 1 (SAA1), was confirmed to be increased specifically in the plasma of patients with AIH compared to other chronic hepatitis. Different plasma levels of SAA1 were also found related to different grades of inflammation and stages of fibrosis in the liver of patients with AIH. Conclusions Our study is the first to describe the proteomics analysis of a true sense of AIH mouse model, which is beneficial for a better understanding of AIH pathogenesis and identifying potential biomarkers for its clinical diagnosis. |
topic |
Autoimmune hepatitis Mouse model Proteome KEGG SAA1 |
url |
https://doi.org/10.1186/s12967-019-02180-3 |
work_keys_str_mv |
AT hanwang plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel AT weiyan plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel AT zuohuafeng plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel AT yuangao plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel AT liuzhang plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel AT xinxiafeng plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel AT deantian plasmaproteomicanalysisofautoimmunehepatitisinanimprovedaihmousemodel |
_version_ |
1724343139089514496 |