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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yuanqin Duan, Zhiwei Chen, Hu Li, Wei Shen, Yi Zeng, Mingli Peng, Peng Hu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tenofovir disoproxil fumarate chronic liver diseases non-antiviral effect immunity inflammation metabolism Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6e4a8f440d0e4eb085c3196e72d1f352
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6e4a8f440d0e4eb085c3196e72d1f352
record_format	dspace
spelling	oai:doaj.org-article:6e4a8f440d0e4eb085c3196e72d1f3522021-11-16T06:31:15ZPotential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model2296-889X10.3389/fmolb.2021.763150https://doaj.org/article/6e4a8f440d0e4eb085c3196e72d1f3522021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.763150/fullhttps://doaj.org/toc/2296-889XAccumulating 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.Yuanqin DuanZhiwei ChenHu LiWei ShenYi ZengMingli PengPeng HuFrontiers Media S.A.articletenofovir disoproxil fumaratechronic liver diseasesnon-antiviral effectimmunityinflammationmetabolismBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tenofovir disoproxil fumarate chronic liver diseases non-antiviral effect immunity inflammation metabolism Biology (General) QH301-705.5
spellingShingle	tenofovir disoproxil fumarate chronic liver diseases non-antiviral effect immunity inflammation metabolism Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	potential molecular targets of tenofovir disoproxil fumarate for alleviating chronic liver diseases via a non-antiviral effect in a normal mouse model
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6e4a8f440d0e4eb085c3196e72d1f352
work_keys_str_mv	AT yuanqinduan potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel AT zhiweichen potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel AT huli potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel AT weishen potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel AT yizeng potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel AT minglipeng potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel AT penghu potentialmoleculartargetsoftenofovirdisoproxilfumarateforalleviatingchronicliverdiseasesviaanonantiviraleffectinanormalmousemodel
_version_	1718426671387770880

Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model

Ejemplares similares