ArticleGastroenterology2015
Fibroblast Growth Factor Signaling Controls Liver Size in Mice With Humanized Livers.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Bile Acids and FXR: Novel Targets for Liver Diseases.Frontiers in medicine · 2020Pooled it
- A humanized mouse model of APOB deficiency recapitulates hypobetalipoproteinemia.Journal of lipid research · 2026Article
- The Role of Gut Microbiota in Liver Regeneration After Partial Hepatectomy: New Evidence From Animal and Human Studies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Review
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025Review
- Targeted therapy for liver cancer: Current status and future directions.BioImpacts : BI · 2025Review
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Comprehensive gene profiling of the metabolic landscape of humanized livers in mice.Journal of hepatology · 2024Article
- Targeting the FGF19-FGFR4 pathway for cholestatic, metabolic, and cancerous diseases.Journal of internal medicine · 2024Review
- Review
- Gut-liver axis: barriers and functional circuits.Nature reviews. Gastroenterology & hepatology · 2023Review
- IL-6-GP130 signaling protects human hepatocytes against lipid droplet accumulation in humanized liver models.Science advances · 2023Article
- Behavioral and cognitive performance of humanized APOEε3/ε3 liver mice in relation to plasma apolipoprotein E levels.Scientific reports · 2023Article
- Evidence forbioRxiv : the preprint server for biology · 2023Article
- Review
- Human hepatocyte PNPLA3-148M exacerbates rapid non-alcoholic fatty liver disease development in chimeric mice.Cell reports · 2022Article
- Pregnancy and weaning regulate human maternal liver size and function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers.Biomedicines · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe ratio of liver size to body weight (hepatostat) is tightly controlled, but little is known about how the physiologic functions of the liver help determine its size. Livers of mice repopulated with human hepatocytes (humanized livers) grow to larger than normal; the human hepatocytes do not recognize the fibroblast growth factor (FGF)-15 produced by mouse intestine. This results in up-regulation of bile acid synthesis in the human hepatocytes and enlargement of the bile acid pool. We investigated whether abnormal bile acid signaling affects the hepatostat in mice.
methodsWe crossed Fah(-/-), Rag2(-/-), Il2r(-/-) mice with nonobese diabetic mice to create FRGN mice, whose livers can be fully repopulated with human hepatocytes. We inserted the gene for human FGF19 (ortholog to mouse Fgf15), including regulatory sequences, into the FRGN mice to create FRGN19(+) mice. Livers of FRGN19(+) mice and their FRGN littermates were fully repopulated with human hepatocytes. Liver tissues were collected and bile acid pool sizes and RNA sequences were analyzed and compared with those of mice without humanized livers (controls).
resultsLivers were larger in FRGN mice with humanized livers (13% of body weight), compared with control FRGN mice; they also had much larger bile acid pools and aberrant bile acid signaling. Livers from FRGN19(+) normalized to 7.8% of body weight, and their bile acid pool and signaling more closely resembled that of control FRGN19(+) mice. RNA sequence analysis showed activation of the Hippo pathway, and immunohistochemical and transcription analyses revealed increased hepatocyte proliferation, but not apoptosis, in the enlarged humanized livers of FRGN mice. Cell sorting experiments showed that although healthy human liver does not produce FGF19, nonparenchymal cells from cholestatic livers produce FGF19.
conclusionsIn mice with humanized livers, expression of an FGF19 transgene corrects bile acid signaling defects, resulting in normalization of bile acid synthesis, the bile acid pool, and liver size. These findings indicate that liver size is, in part, regulated by the size of the bile acid pool that the liver must circulate.
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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.