Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model
Accumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to iden...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.763150/full |
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| author | Yuanqin Duan Zhiwei Chen Hu Li Wei Shen Yi Zeng Mingli Peng Peng Hu |
| author_facet | Yuanqin Duan Zhiwei Chen Hu Li Wei Shen Yi Zeng Mingli Peng Peng Hu |
| author_sort | Yuanqin Duan |
| collection | DOAJ |
| description | Accumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to identify the molecular targets and potential mechanism of TDF itself in ameliorating CLDs. RNA-sequencing was performed on mouse liver tissues treated with TDF or normal saline. Then the differentially expressed genes (DEGs) were screened, and enrichment analyses of the function and signaling pathways of DEGs were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape. Next, protein-protein interaction (PPI) networks were constructed and module analyses were utilized to identify significant genes. Subsequently, the DisGeNET platform was used to identify the potential target genes of TDF in mitigating these diseases. Finally, prediction of the transcription factors (TFs) and microRNAs (miRNAs) of the target genes was done to conjecture the underlying mechanism by which TDF relieved CLDs. As a result, a total of 854 DEGs were identified, and the DEGs were involved mainly in “immunity,” “inflammation,” and “metabolism” processes. In addition, 50 significant genes were obtained via PPI construction and module analyses. Furthermore, by means of DisGeNET, 19 genes (Adra2a, Cxcl1, Itgam, Cxcl2, Ccr1, Ccl5, Cxcl5, Fabp5, Sell, Lilr4b, Ccr2, Tlr2, Lilrb4a, Tnf, Itgb2, Lgals3, Cxcr4, Sucnr1, and Mme) were identified to be associated with nine CLDs. Finally, 34 miRNAs (especially mmu-miR-155-5p) and 12 TFs (especially Nfkb1) were predicted to be upstream of the nine target genes (Cxcl1, Cxcl2, Ccl5, Ccr2, Sell, Tlr2, Tnf, Cxcr4, and Mme) of TDF in ameliorating CLDs. In conclusion, our study suggests that TDF have the potential to ameliorate CLDs independently of its antiviral activity by affecting the expression of genes involved in hepatic immune, inflammatory, and metabolic processes via mmu-miR-155-5p-NF-κB signaling. These findings provided prima facie evidence for using TDF in CHB patients with concurrent CLDs. |
| first_indexed | 2024-12-18T01:26:26Z |
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| id | doaj.art-6e4a8f440d0e4eb085c3196e72d1f352 |
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| language | English |
| last_indexed | 2024-12-18T01:26:26Z |
| publishDate | 2021-11-01 |
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| spelling | doaj.art-6e4a8f440d0e4eb085c3196e72d1f3522022-12-21T21:25:43ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-11-01810.3389/fmolb.2021.763150763150Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse ModelYuanqin DuanZhiwei ChenHu LiWei ShenYi ZengMingli PengPeng HuAccumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to identify the molecular targets and potential mechanism of TDF itself in ameliorating CLDs. RNA-sequencing was performed on mouse liver tissues treated with TDF or normal saline. Then the differentially expressed genes (DEGs) were screened, and enrichment analyses of the function and signaling pathways of DEGs were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape. Next, protein-protein interaction (PPI) networks were constructed and module analyses were utilized to identify significant genes. Subsequently, the DisGeNET platform was used to identify the potential target genes of TDF in mitigating these diseases. Finally, prediction of the transcription factors (TFs) and microRNAs (miRNAs) of the target genes was done to conjecture the underlying mechanism by which TDF relieved CLDs. As a result, a total of 854 DEGs were identified, and the DEGs were involved mainly in “immunity,” “inflammation,” and “metabolism” processes. In addition, 50 significant genes were obtained via PPI construction and module analyses. Furthermore, by means of DisGeNET, 19 genes (Adra2a, Cxcl1, Itgam, Cxcl2, Ccr1, Ccl5, Cxcl5, Fabp5, Sell, Lilr4b, Ccr2, Tlr2, Lilrb4a, Tnf, Itgb2, Lgals3, Cxcr4, Sucnr1, and Mme) were identified to be associated with nine CLDs. Finally, 34 miRNAs (especially mmu-miR-155-5p) and 12 TFs (especially Nfkb1) were predicted to be upstream of the nine target genes (Cxcl1, Cxcl2, Ccl5, Ccr2, Sell, Tlr2, Tnf, Cxcr4, and Mme) of TDF in ameliorating CLDs. In conclusion, our study suggests that TDF have the potential to ameliorate CLDs independently of its antiviral activity by affecting the expression of genes involved in hepatic immune, inflammatory, and metabolic processes via mmu-miR-155-5p-NF-κB signaling. These findings provided prima facie evidence for using TDF in CHB patients with concurrent CLDs.https://www.frontiersin.org/articles/10.3389/fmolb.2021.763150/fulltenofovir disoproxil fumaratechronic liver diseasesnon-antiviral effectimmunityinflammationmetabolism |
| spellingShingle | Yuanqin Duan Zhiwei Chen Hu Li Wei Shen Yi Zeng Mingli Peng Peng Hu Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model Frontiers in Molecular Biosciences tenofovir disoproxil fumarate chronic liver diseases non-antiviral effect immunity inflammation metabolism |
| title | Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model |
| title_full | Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model |
| title_fullStr | Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model |
| title_full_unstemmed | Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model |
| title_short | Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model |
| title_sort | potential molecular targets of tenofovir disoproxil fumarate for alleviating chronic liver diseases via a non antiviral effect in a normal mouse model |
| topic | tenofovir disoproxil fumarate chronic liver diseases non-antiviral effect immunity inflammation metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.763150/full |
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