Yes-associated protein is involved in proliferation and differentiation during postnatal liver development
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It is known that the liver undergoes size increase and differentiation simultaneously during the postnatal period. Cells in the liver undergo a period of well-controlled proliferation to achieve the adult liver-to-body weight ratio. The postnatal liver growth is also accompanied by simultaneous hepatic differentiation. However, the mechanisms of liver size regulation and differentiation are not completely clear. Herein we report that yes-associated protein (Yap), the downstream effector of the Hippo Kinase signaling pathway, plays a role in liver size regulation and differentiation during the postnatal liver growth period. Postnatal liver growth was studied in C57BL/6 mice over a time course of postnatal days (PND) 0-30. Analysis of nuclear Yap by Western blot indicated peak Yap activation between PND15-20, which coincided with increased cyclin D1 expression and liver cell proliferation. Analysis of postnatal liver development in Yap(+/-) mice revealed a significant decrease in the liver-to-body weight ratio compared with Yap(+/+) mice at PND15 and -30. Yap(+/-) mice exhibited a significant decrease in postnatal liver cell proliferation, but no change in apoptosis was observed. Furthermore, global gene expression analysis of Yap(+/-) livers revealed a role of Yap in regulation of genes involved in bile acid metabolism, retinoic acid metabolism, ion transport, and extracellular matrix proteins. Taken together, these data indicate that Yap plays a role in both cell proliferatio…
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A previous gene-expression analysis of postnatal heterozygous YAP mice indicated that ECM proteins become deregulated.
“Furthermore, a previous gene-expression analysis of postnatal heterozygous YAP mice indicated that ECM proteins become deregulated (Septer et al., 2012).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Septer et al., 2012
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- Authors
- Septer, S., Edwards, G., Gunewardena, S., Wolfe, A., Li, H., Daniel, J., & Apte, U.
- Affiliations
- Children's Mercy Hospital (US)
- Department of Pharmacology, Toxicology and Therapeutics and
- University of Kansas Medical Center (US)
- Corresponding author
- Apte, Udayan
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2012-03-01
- Volume
- 302
- Issue
- 5
- Pages
- G493-G503
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- PMC
- PMC3311431
- OpenAlex
- W2125417595
- Cited by
- 43
- References
- 18
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 2 · 2014: 4
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Kansas
- National Center for Research Resources (5 P20 RR-021940-03, P20RR021940, RR016475, P20RR016475)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-02528)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- YAP, Hippo signaling pathway, postnatal liver development, liver growth, liver cell proliferation, hepatic differentiation, liver-to-body weight ratio, cyclin D1, bile acid metabolism, retinoic acid metabolism, extracellular matrix
- MeSH terms
- YAP-Signaling Proteins, Animals, Bile Acids and Salts, Cell Differentiation, Female, Liver, Male, Mice, Inbred C57BL, Organ Size, Phosphoproteins, Tretinoin, Ion Transport, Apoptosis, Cell Cycle Proteins, Gene Expression Profiling, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice
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