ArticleHepatology (Baltimore, Md.)2013
Bile salt export pump is dysregulated with altered farnesoid X receptor isoform expression in patients with hepatocellular carcinoma.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 83 citations in OpenAlex.
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Transcriptional regulation of ubiquitin specific peptidase 2b by farnesoid X receptor and its implications in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2026Article
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Evaluation of the significance of single nucleotide polymorphisms of theClinical and experimental hepatology · 2024Article
- Article
- Interpretation of Farnesoid X Receptor Immunohistochemical Expression in Discriminating Hepatocellular Carcinoma from Its Non-Neoplastic Mimics as an Adjunct to Glypican 3.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- A Dual Coverage Monitoring of the Bile Acids Profile in the Liver-Gut Axis throughout the Whole Inflammation-Cancer Transformation Progressive: Reveal Hepatocellular Carcinoma Pathogenesis.International journal of molecular sciences · 2023Article
- Dysregulation and oncogenic activities of ubiquitin specific peptidase 2a in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2023Article
- New insights into the bile acid-based regulatory mechanisms and therapeutic perspectives in alcohol-related liver disease.Cellular and molecular life sciences : CMLS · 2022Review
- Hepatic Transcriptome Analysis Provides New Insight into the Lipid-Reducing Effect of Dietary Taurine in High-Fat Fed Groupers (Metabolites · 2022Article
- Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism.Molecular and cellular endocrinology · 2022Review
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
- Mechanism and Active Components of Qingre Lidan Tablets Alleviate Intrahepatic Cholestasis by Activating the FarnesoidEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- Bile Acids, Their Receptors, and the Gut Microbiota.Physiology (Bethesda, Md.) · 2021Review
- Article
- Dysregulation and activities of ubiquitin specific peptidase 2b in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2021Article
- Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development.Hepatology communications · 2018Article
- Pediatric hepatocellular carcinoma.World journal of gastroenterology · 2018Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledAs a canalicular bile acid effluxer, the bile salt export pump (BSEP) plays a vital role in maintaining bile acid homeostasis. BSEP deficiency leads to severe cholestasis and hepatocellular carcinoma (HCC) in young children. Regardless of the etiology, chronic inflammation is the common pathological process for HCC development. Clinical studies have shown that bile acid homeostasis is disrupted in HCC patients with elevated serum bile acid level as a proposed marker for HCC. However, the underlying mechanisms remain largely unknown. In this study, we found that BSEP expression was severely diminished in HCC tissues and markedly reduced in adjacent nontumor tissues. In contrast to mice, human BSEP was regulated by farnesoid X receptor (FXR) in an isoform-dependent manner. FXR-α2 exhibited a much more potent activity than FXR-α1 in transactivating human BSEP in vitro and in vivo. The decreased BSEP expression in HCC was associated with altered relative expression of FXR-α1 and FXR-α2. FXR-α1/FXR-α2 ratios were significantly increased, with undetectable FXR-α2 expression in one third of the HCC tumor samples. A similar correlation between BSEP and FXR isoform expression was confirmed in hepatoma Huh7 and HepG2 cells. Further studies showed that intrahepatic proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), were significantly elevated in HCC tissues. Treatment of Huh7 cells with IL-6 and TNF-α resulted in a marked increase in FXR-α1/FXR-α2 ratio, concurrent with a significant decrease in BSEP expression.
conclusionBSEP expression is severely diminished in HCC patients associated with alteration of FXR isoform expression induced by inflammation. Restoration of BSEP expression through suppressing inflammation in the liver may reestablish bile acid homeostasis.
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