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Sodium taurocholate co-transporting polypeptide deficiency attenuates hepatocarcinogenesis in mice

ABSTRACT: Sodium taurocholate co-transporting polypeptide deficiency attenuates hepatocarcinogenesis in mice

PROVIDER: PRJNA655900 | ENA |

REPOSITORIES: ENA

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Sodium taurocholate co-transporting polypeptide deficiency attenuates hepatocarcinogenesis in mice

Project description:Sodium taurocholate co-transporting polypeptide (NTCP) is a liver specific bile acid (BA) transporter; this transporter also serves as a functional receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV). Here, we generated mouse models to investigate the role of NTCP in hepatocarcinogenesis. We report that NTCP-deficient (Slc10a1-/-) mice with long-term hypercholanemia do not develop spontaneous hepatocellular carcinoma (HCC). Using a diethylnitrosamine (DEN)-induced mouse model of HCC, we found that Slc10a1-/- mice exhibited fewer liver tumors, while transgenic mice constitutively overexpressing mouse NTCP in hepatocytes Tg(mNTCP-C9) experienced increased tumor burdens. Intriguingly, the subset of male Slc10a1-/- mice with hypercholanemia exhibited a hepatic female-biased gene expression. Importantly, a majority of the human homologs of genes with significantly hepatic female-biased expression were found to be correlated with improved prognosis in human patients with liver cancer. Our ﬁndings indicate that pharmacological manipulation of NTCP function can have a clinical impact on decreasing risk of development or decreasing risk of death liver cancer.

2025-08-01 | GSE155870 | GEO

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

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

| PRJNA510995 | ENA

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.

2019-06-13 | GSE124214 | GEO

microRNA-6126 downregulates NTCP expression through decreasing stability of its messenger RNA in hepatocyte

Project description:miR-6126 downregulated expression level of sodium taurocholate cotransporting polypeptide (NTCP), a host cell receptor required for hepatitis B virus (HBV) entry.

2022-08-01 | GSE180543 | GEO

Calnexin depletion by ER-stress during cholestasis inhibits the Na+-taurocholate Cotransporting Polypeptide (NTCP)

Project description:Impaired bile flow (cholestasis) leads to transcriptional downregulation of the bile acid importer Na+-taurocholate co-transporting protein (NTCP) and to ER-stress in the liver. Here, we show that ER-stress induction strongly reduces NTCP protein expression, plasma membrane abundance and NTCP-mediated bile acid uptake. This is not controlled via a single specific UPR-pathway but mainly depends on the interaction of NTCP with calnexin, an ER chaperone involved in folding of N-glycosylated proteins. In mice, expression of both Ntcp and calnexin was reduced by thapsigargin-induced ER-stress. Calnexin downregulation in HepG2 and U2OS cells results in a decreased NTCP expression and a reduced bile acid uptake. Calreticulin shows partial functional redundancy with calnexin as it also interacts with NTCP, and is downregulated upon ER-stress, but specifically in calnexin-depleted cells. In conclusion, ER stress-induced downregulation of calnexin provides an additional mechanism to dampen NTCP-mediated bile acid uptake during cholestasis.

2019-01-07 | PXD007948 | Pride

A substrate pharmacophore for the human sodium taurocholate co-transporting polypeptide.

Project description: Not available

| S-EPMC4430447 | biostudies-literature

Neuropilin-1 is a novel host factor facilitating the entry of hepatitis B virus

Project description:Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit diversely susceptibilities to HBV infection. In this study, we identified multiple membrame proteins played a critical role in facilitating HBV infection in liver biopsy obtained from children with chronic hepatitis B by using singlecell RNA sequencing (scRNA-seq).

2026-05-31 | GSE264335 | GEO

Monozygotic Twins Suffering From Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report.

Project description: Not available

| S-EPMC6256173 | biostudies-literature

Non-coding small RNA expression analysis of rat pancreatic acinar cells(AR42J) treated with sodium taurocholate

Project description:Non-coding small RNA expression analysis of rat pancreatic acinar cells(AR42J) treated with sodium taurocholate

| PRJNA750677 | ENA

Blocking Sodium-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice.

Project description: Not available

| S-EPMC7003915 | biostudies-literature