ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2008
PI3K/Akt activation is critical for early hepatic regeneration after partial hepatectomy.
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 49 papers.
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Who cites it
49 citing papers in PubMed, 106 citations in OpenAlex.
- Xanthoxylin Protects Against Alcoholic Liver Injury via the EGFR/AKT Pathway: A Combined In Silico and In Vitro Study.Molecules (Basel, Switzerland) · 2026Article
- Hepatotoxic Mechanisms of Polyethylene Terephthalate Microplastics Revealed by Network Toxicology, Molecular Docking, and In Vivo Validation.International journal of molecular sciences · 2026Article
- VIRMA-mediated SHQ1 m6A modification enhances liver regeneration through an HNRNPA2B1-dependent mechanism.Acta pharmaceutica Sinica. B · 2025Article
- Pharmacological and therapeutic effects of natural products on liver regeneration-a comprehensive research.Chinese medicine · 2025Review
- Article
- Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice.International journal of molecular medicine · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Liver diseases: epidemiology, causes, trends and predictions.Signal transduction and targeted therapy · 2025Review
- Integrative network pharmacology, metabolomics and gut flora studies reveal mechanisms of action ofFrontiers in microbiology · 2025Article
- Dietary Linoleic Acid: An Omega-6 Fatty Acid Essential for Liver Regeneration in Buffalo Rats.Comparative medicine · 2023Article
- Therapeutic strategies to improve liver regeneration after hepatectomy.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Mitigation of acetaminophen-induced liver toxicity by the novel phosphatidylinositol 3-kinase inhibitor alpelisib.Frontiers in pharmacology · 2023Article
- PARK7 deficiency inhibits fatty acid β-oxidation via PTEN to delay liver regeneration after hepatectomy.Clinical and translational medicine · 2022Article
- Effects of Substance P for Liver Regeneration in Rat Hepatectomy Models: A Preliminary Experimental Animal Study.Annals of transplantation · 2022Article
- Liver Regeneration: Changes in Oxidative Stress, Immune System, Cytokines, and Epigenetic Modifications Associated with Aging.Oxidative medicine and cellular longevity · 2022Review
- Liver regeneration biology: Implications for liver tumour therapies.World journal of clinical oncology · 2021Review
- Genetic and Cellular Contributions to Liver Regeneration.Cold Spring Harbor perspectives in biology · 2021Article
- ADAM10 and ADAM17 regulate EGFR, c-Met and TNF RI signalling in liver regeneration and fibrosis.Scientific reports · 2021Article
- PI3K Plays an Essential Role in Planarian Regeneration and Tissue Maintenance.Frontiers in cell and developmental biology · 2021Article
- Liver Regeneration after Hepatectomy and Partial Liver Transplantation.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic resection is associated with rapid proliferation and regeneration of the remnant liver. Phosphatidylinositol 3-kinase (PI3K), composed of a p85alpha regulatory and a p110alpha catalytic subunit, participates in multiple cellular processes, including cell growth and survival; however, the role of PI3K in liver regeneration has not been clearly delineated. In this study, we used the potent PI3K inhibitor wortmannin and small interfering RNA (siRNA) targeting the p85alpha and p110alpha subunits to determine whether total or selective PI3K inhibition would abrogate the proliferative response of the liver after partial hepatectomy in mice. Hepatic resection is associated with an induction in PI3K activity; total PI3K blockade with wortmannin and selective inhibition of p85alpha or p110alpha with siRNA resulted in a significant decrease in hepatocyte proliferation, especially at the earliest time points. Fewer macrophages and Kupffer cells were present in the regenerating liver of mice treated with wortmannin or siRNA to p85alpha or p110alpha, as reflected by a paucity of F4/80-positive cells. Additionally, PI3K inhibition led to an aberrant architecture in the regenerating hepatocytes characterized by vacuolization, lipid deposition, and glycogen accumulation; these changes were not noted in the sham livers. Our data demonstrate that PI3K/Akt pathway activation plays a critical role in the early regenerative response of the liver after resection; inhibition of this pathway markedly abrogates the normal hepatic regenerative response, most likely by inhibiting macrophage infiltration and cytokine elaboration and thus hepatocyte priming for replication.
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