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Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

ABSTRACT: Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

PROVIDER: PRJNA510995 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8360780_1.fastq.gz	Fastqsanger.gz
	SRR8360780_2.fastq.gz	Fastqsanger.gz
	SRR8360790.fastq.gz	Fastqsanger.gz
	SRR8360800.fastq.gz	Fastqsanger.gz
	SRR8360771_1.fastq.gz	Fastqsanger.gz

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Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

Project description:Purpose: To decipher the biochemical basis for the declining of total bile acids (TBA) levels in the late age of Slc10a1-/- mice, we performed a serial liver RNA-Seq analysis of mRNA expression with male mice at different ages. Methods: Liver mRNA profiles of 4-week, 8-week, 20-month-old wild-type (WT) and sodium taurocholate cotransporting polypeptide knockout (Slc10a1-/-) mice were generated by deep sequencing, in triplicate, quadruplicate or sextuplicate, using Illumina Hiseq-2500 platform. Clean mRNA-seq reads were aligned to the mouse reference genome (GRCm38) with TopHat (v2.0.13), guided by Ensembl gene annotation v83. Only uniquely aligned and properly paired reads were retained for further analysis. Gene-level read counts were calculated with HTseq (v0.6.1p1) with the union mode. Genes with less than a total of 11 non-normalized reads across all samples were excluded. Data normalization and statistical analysis of differential expression were performed with the DEseq2 (v1.10.0) R package. Pair-wise Spearman correlation between samples across all quantified genes used for hierarchical clustering. Results: At 4 weeks and 8 weeks, WT and Slc10a1-/- mice exhibited clear different pattern in terms of transcriptome similarity and were well separated, however, the difference was indistinguishable at 20 months.And changes of pathways involved in the metabolism of xenobiotics in Slc10a1-/- mice. Conclusions: Our study reveal that enhanced BA sulfation is a major mechanism for BA detoxification and elimination in Slc10a1-/- mice with hypercholanemia.

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Transcriptome profiles of primary human hepatocytes treated with HBV preS1 peptide with or without bile acids

Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acids-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acids uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acids metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.

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Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA in shock experiments as well as during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection.

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Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection

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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

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