ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2008
beta-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 87 citations in OpenAlex.
- Nanocellulose Alleviates Intrahepatic Cholestasis of Pregnancy via Gut Microbiota-Mediated Bile Acid Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unraveling the Pathophysiology of Irritable Bowel Syndrome: Mechanisms and Insights.International journal of molecular sciences · 2025Review
- Associations of serum Klotho with diabetic kidney disease prevalence and mortality: insights from a nationally representative U.S. cohort.Diabetology & metabolic syndrome · 2025Article
- Signaling of Mitogenic and Metabolic Activities by Fibroblast Growth Factors.Journal of cellular signaling · 2025Article
- High-Fat Diet-Induced Decreased Circulating Bile Acids Contribute to Obesity Associated with Gut Microbiota in Mice.Foods (Basel, Switzerland) · 2024Article
- Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho.Frontiers in endocrinology · 2023Review
- Modulation of gut microbiota and intestinal immune response in gilthead seabream (Frontiers in microbiology · 2023Article
- Review
- Bile Acid and Gut Microbiota in Irritable Bowel Syndrome.Journal of neurogastroenterology and motility · 2022Review
- Review
- Review article: therapeutic aspects of bile acid signalling in the gut-liver axis.Alimentary pharmacology & therapeutics · 2021Review
- The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Gut Microbiota in Liver Disease: What Do We Know and What Do We Not Know?Physiology (Bethesda, Md.) · 2020Review
- Impaired Intestinal Farnesoid X Receptor Signaling in Cystic Fibrosis Mice.Cellular and molecular gastroenterology and hepatology · 2020Article
- Article
- Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?Therapeutic advances in medical oncology · 2020Review
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- Enhanced Microbial Bile Acid Deconjugation and Impaired Ileal Uptake in Pregnancy Repress Intestinal Regulation of Bile Acid Synthesis.Hepatology (Baltimore, Md.) · 2019Article
- Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption.Gastroenterology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
beta-Klotho, a newly described membrane protein, regulates bile acid synthesis. Fibroblast growth factor-15 (FGF-15) and FGF receptor-4 (FGFR4) knockout mice share a similar phenotype with beta-Klotho-deficient mice. FGF-15 secretion by the intestine regulates hepatic bile acid biosynthesis. The effects of beta-Klotho and FGF-15 on the ileal apical sodium bile transporter (ASBT) are unknown. beta-Klotho siRNA treatment of the mouse colon cancer cell line, CT-26, and the human intrahepatic biliary epithelial cells (HIBEC) resulted in upregulation of endogenous ASBT expression that was associated with reduced expression of the farnesoid X receptor (FXR) and the short heterodimer partner (SHP). Silencing beta-Klotho activated the ASBT promoter in CT-26, Mz-ChA-1 (human cholangiocarcinoma), and HIBEC cells. Site-directed mutagenesis of liver receptor homolog-1 (mouse) or retinoic acid receptor/retinoid X receptor (RAR/RXR) (human) cis-elements attenuated the basal activity of the ASBT promoter and abrogated its response to beta-Klotho silencing. siSHP, siFXR, or dominant-negative FXR treatment also eliminated the beta-Klotho response. FGF-15 secretion into cell culture media by CT-26 cells was diminished after siFGF-15 or sibeta-Klotho treatment and enhanced by chenodeoxycholic acid. Exogenous FGF-19 repressed ASBT protein expression in mouse ileum, gallbladder, and in HIBEC and repressed ASBT promoter activity in Caco-2, HIBEC, and Mz-ChA-1 cells. Promoter repression was dependent on the expression of FGFR4. These results indicate that both beta-Klotho and FGF-15/19 repress ASBT in enterocytes and cholangiocytes. These novel signaling pathways need to be considered in analyzing bile acid homeostasis.
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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.