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Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration
Alcohol abuse can lead to alcoholic hepatitis (AH), a worldwide public health issue with high morbidity and mortality. Here, we identified apolipoprotein A-IV (APOA4) as a biomarker and potential therapeutic target for AH. APOA4 expression was detected by Gene Expression Omnibus (GEO) databases, Imm...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820766/ https://www.ncbi.nlm.nih.gov/pubmed/36614113 http://dx.doi.org/10.3390/ijms24010670 |
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author | Li, Wan-Hong Zhang, Li Li, Yue-Ying Wang, Xin-Yue Li, Jin-Liang Zhao, Shu-Ning Ni, Ming-Qi Li, Qian Sun, Hui |
author_facet | Li, Wan-Hong Zhang, Li Li, Yue-Ying Wang, Xin-Yue Li, Jin-Liang Zhao, Shu-Ning Ni, Ming-Qi Li, Qian Sun, Hui |
author_sort | Li, Wan-Hong |
collection | PubMed |
description | Alcohol abuse can lead to alcoholic hepatitis (AH), a worldwide public health issue with high morbidity and mortality. Here, we identified apolipoprotein A-IV (APOA4) as a biomarker and potential therapeutic target for AH. APOA4 expression was detected by Gene Expression Omnibus (GEO) databases, Immunohistochemistry, and qRT-PCR in AH. Bioinformatics Methods (protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Set Enrichment Analysis (GSEA) were used to show down-stream gene and pathways of APOA4 in AH. AML-12 cells were used to evaluate the biological function of APOA4 using an ELISA kit (AST, ALT, and IL-1β) and flow cytometry (ROS activity). Both in vivo and in vitro, APOA4 expression was significantly elevated in the AH model induced by alcohol (ETOH). AML-12 cell damage was specifically repaired by APOA4 deficiency, while AST, ALT, and IL-1β activity that was increased by ETOH (200 µmol, 12 h) were suppressed. APOA4 inhibition increased intracellular ROS induced by ETOH, which was detected by flow cytometry. Functional and PPI network analyses showed Fcgamma receptor (FCGR) and platelet activation signaling were potential downstream pathways. We identified CIDEC as a downstream gene of APOA4. The CIDEC AUC values for the ROC curves were 0.861. At the same time, APOA4 silencing downregulated the expression of CIDEC, whereas the knockdown of CIDEC did not influence the expression of APOA4 in AML-12 cells. Collectively, APOA4 regulates CIDEC expression and immune cell infiltration and may hold great potential as a biomarker and therapeutic target for AH. |
format | Online Article Text |
id | pubmed-9820766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98207662023-01-07 Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration Li, Wan-Hong Zhang, Li Li, Yue-Ying Wang, Xin-Yue Li, Jin-Liang Zhao, Shu-Ning Ni, Ming-Qi Li, Qian Sun, Hui Int J Mol Sci Article Alcohol abuse can lead to alcoholic hepatitis (AH), a worldwide public health issue with high morbidity and mortality. Here, we identified apolipoprotein A-IV (APOA4) as a biomarker and potential therapeutic target for AH. APOA4 expression was detected by Gene Expression Omnibus (GEO) databases, Immunohistochemistry, and qRT-PCR in AH. Bioinformatics Methods (protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Set Enrichment Analysis (GSEA) were used to show down-stream gene and pathways of APOA4 in AH. AML-12 cells were used to evaluate the biological function of APOA4 using an ELISA kit (AST, ALT, and IL-1β) and flow cytometry (ROS activity). Both in vivo and in vitro, APOA4 expression was significantly elevated in the AH model induced by alcohol (ETOH). AML-12 cell damage was specifically repaired by APOA4 deficiency, while AST, ALT, and IL-1β activity that was increased by ETOH (200 µmol, 12 h) were suppressed. APOA4 inhibition increased intracellular ROS induced by ETOH, which was detected by flow cytometry. Functional and PPI network analyses showed Fcgamma receptor (FCGR) and platelet activation signaling were potential downstream pathways. We identified CIDEC as a downstream gene of APOA4. The CIDEC AUC values for the ROC curves were 0.861. At the same time, APOA4 silencing downregulated the expression of CIDEC, whereas the knockdown of CIDEC did not influence the expression of APOA4 in AML-12 cells. Collectively, APOA4 regulates CIDEC expression and immune cell infiltration and may hold great potential as a biomarker and therapeutic target for AH. MDPI 2022-12-30 /pmc/articles/PMC9820766/ /pubmed/36614113 http://dx.doi.org/10.3390/ijms24010670 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Wan-Hong Zhang, Li Li, Yue-Ying Wang, Xin-Yue Li, Jin-Liang Zhao, Shu-Ning Ni, Ming-Qi Li, Qian Sun, Hui Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration |
title | Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration |
title_full | Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration |
title_fullStr | Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration |
title_full_unstemmed | Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration |
title_short | Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration |
title_sort | apolipoprotein a-iv has bi-functional actions in alcoholic hepatitis by regulating hepatocyte injury and immune cell infiltration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820766/ https://www.ncbi.nlm.nih.gov/pubmed/36614113 http://dx.doi.org/10.3390/ijms24010670 |
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