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...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/670 |
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| author | Wan-Hong Li Li Zhang Yue-Ying Li Xin-Yue Wang Jin-Liang Li Shu-Ning Zhao Ming-Qi Ni Qian Li Hui Sun |
| author_facet | Wan-Hong Li Li Zhang Yue-Ying Li Xin-Yue Wang Jin-Liang Li Shu-Ning Zhao Ming-Qi Ni Qian Li Hui Sun |
| author_sort | Wan-Hong Li |
| collection | DOAJ |
| 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 <i>CIDEC</i> 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 <i>CIDEC</i>, whereas the knockdown of <i>CIDEC</i> did not influence the expression of APOA4 in AML-12 cells. Collectively, APOA4 regulates <i>CIDEC</i> expression and immune cell infiltration and may hold great potential as a biomarker and therapeutic target for AH. |
| first_indexed | 2024-03-11T09:58:54Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:58:54Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-68d6a09da07f4bfd939dd07c69d2fefa2023-11-16T15:36:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124167010.3390/ijms24010670Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell InfiltrationWan-Hong Li0Li Zhang1Yue-Ying Li2Xin-Yue Wang3Jin-Liang Li4Shu-Ning Zhao5Ming-Qi Ni6Qian Li7Hui Sun8Pharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaPharmaceutical Experiment Teaching Center, College of Pharmacy, Harbin Medical University, Harbin 150081, ChinaAlcohol 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 <i>CIDEC</i> 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 <i>CIDEC</i>, whereas the knockdown of <i>CIDEC</i> did not influence the expression of APOA4 in AML-12 cells. Collectively, APOA4 regulates <i>CIDEC</i> expression and immune cell infiltration and may hold great potential as a biomarker and therapeutic target for AH.https://www.mdpi.com/1422-0067/24/1/670alcoholic hepatitisapolipoprotein A-IVinflammationimmune cell infiltrationCIDEC |
| spellingShingle | Wan-Hong Li Li Zhang Yue-Ying Li Xin-Yue Wang Jin-Liang Li Shu-Ning Zhao Ming-Qi Ni Qian Li Hui Sun Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration International Journal of Molecular Sciences alcoholic hepatitis apolipoprotein A-IV inflammation immune cell infiltration CIDEC |
| 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 | alcoholic hepatitis apolipoprotein A-IV inflammation immune cell infiltration CIDEC |
| url | https://www.mdpi.com/1422-0067/24/1/670 |
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