ArticleToxicology and applied pharmacology2013
Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice.
Article in Toxicology and applied pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Bile acid metabolism and hepatocellular carcinoma: mechanisms of drug resistance and intervention strategies.Precision clinical medicine · 2025Review
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- Liver-specific Nr1h4 deletion in mice with human-like bile acid composition causes severe liver injury.Journal of lipid research · 2025Article
- A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.International journal of molecular sciences · 2024Review
- The contributions of bacteria metabolites to the development of hepatic encephalopathy.Liver research (Beijing, China) · 2023Article
- The Role of Bile Acids in the Human Body and in the Development of Diseases.Molecules (Basel, Switzerland) · 2022Review
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
- Cross-Platform in-silico Analyses Exploring Tumor Immune Microenvironment with Prognostic Value in Triple-Negative Breast Cancer.Breast cancer (Dove Medical Press) · 2022Article
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- Ilexsaponin AFrontiers in pharmacology · 2021Article
- miRNA-382-5p Suppresses the Expression of Farnesoid X Receptor to Promote Progression of Liver Cancer.Cancer management and research · 2021Article
- Regulation of Lung Macrophage Activation and Oxidative Stress Following Ozone Exposure by Farnesoid X Receptor.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- A novel benzamine lead compound of histone deacetylase inhibitor ZINC24469384 can suppresses HepG2 cells proliferation by upregulating NR1H4.Scientific reports · 2019Article
- Regulation of bile acid receptor activityLiver research (Beijing, China) · 2018Article
- Suppression of Hepatic Bile Acid Synthesis by a non-tumorigenic FGF19 analogue Protects Mice from Fibrosis and Hepatocarcinogenesis.Scientific reports · 2018Article
- Update on FXR Biology: Promising Therapeutic Target?International journal of molecular sciences · 2018Review
- Hepatocyte nuclear receptor SHP suppresses inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis.The Journal of biological chemistry · 2018Article
- Nuclear receptors in cancer - uncovering new and evolving roles through genomic analysis.Nature reviews. Genetics · 2018Review
- Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2018Review
- Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.The Journal of pathology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR(-/-) and SHP(-/-) mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR(-/-) mice and therefore, increased SHP expression in FXR(-/-) mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR(-/-) mice with overexpression of SHP in hepatocytes (FXR(-/-)/SHP(Tg)) and determined the contribution of SHP in HCC development in FXR(-/-) mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR(-/-) mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR(-/-) mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.