ArticleProceedings of the National Academy of Sciences of the United States of America2011
Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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
48 citing papers in PubMed, 96 citations in OpenAlex.
- Endothelial nitric oxide signaling in cellular and systemic metabolism.Redox biology · 2026Review
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- The relationship between spontaneous cystic degeneration and pseudocapillarization in sinusoids in the liver of aged Sprague-Dawley rats.Journal of toxicologic pathology · 2025Article
- Comprehensive Review of Future Liver Remnant (FLR) Assessment and Hypertrophy Techniques Before Major Hepatectomy: How to Assess and Manage the FLR.Annals of surgical oncology · 2024Review
- Tryptophan Metabolites in the Progression of Liver Diseases.Biomolecules · 2024Article
- Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation.Cellular & molecular biology letters · 2024Article
- Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice.Nature communications · 2024Article
- Liver organoid culture methods.Cell & bioscience · 2023Review
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Bedside to bench: the outlook for psychedelic research.Frontiers in pharmacology · 2023Review
- Review
- Serotonin in the regulation of systemic energy metabolism.Journal of diabetes investigation · 2022Review
- Understanding the Unique Microenvironment in the Aging Liver.Frontiers in medicine · 2022Review
- Liver regeneration biology: Implications for liver tumour therapies.World journal of clinical oncology · 2021Review
- A narrative review of liver regeneration-from models to molecular basis.Annals of translational medicine · 2021Review
- Till Death Do Us Part-The Multifaceted Role of Platelets in Liver Diseases.International journal of molecular sciences · 2021Review
- The effect of aging on VEGF/VEGFR2 signal pathway genes expression in rat liver sinusoidal endothelial cell.Molecular and cellular biochemistry · 2021Article
- The wHole Story About Fenestrations in LSEC.Frontiers in physiology · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease.Frontiers in physiology · 2020Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of the liver is well-preserved during the aging process, although some evidence suggests that liver regeneration might be impaired with advanced age. We observed a decreased ability of the liver to restore normal volume after partial hepatectomy in elderly mice, and we identified a pathway that rescued regeneration and was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin receptor agonist, reversed the age-related pseudocapillarization of old liver and improved hepatosinusoidal blood flow. After hepatectomy, the open fenestrae were associated with a restored attachment of platelets to endothelium and the initiation of a normal regenerative response, including the up-regulation of essential growth mediators and serotonin receptors. In turn, hepatocyte proliferation recovered along with regain of liver volume and animal survival. DOI operates through the release of VEGF, and its effects could be blocked with anti-VEGF antibodies both in vitro and in vivo. These results suggest that pseudocapillarization in the aged acts as a barrier to liver regeneration. DOI breaks this restraint through an endothelium-dependent mechanism driven by VEGF. This pathway highlights a target for reversing the age-associated decline in the capacity of the liver to regenerate.
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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.