ArticleMolecular and cellular biology2009
The age-associated decline of glycogen synthase kinase 3beta plays a critical role in the inhibition of liver regeneration.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 76 citations in OpenAlex.
- Hematopoietic (stem) cells-The elixir of life?FEBS letters · 2026Review
- RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer's Disease.Current issues in molecular biology · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Transcriptional control of a stem cell factor nucleostemin in liver regeneration and aging.PloS one · 2024Article
- Age-related differences in response to plasma exchange in male rat liver tissues: insights from histopathological and machine-learning assisted spectrochemical analyses.Biogerontology · 2023Article
- Network-level analysis of ageing and its relationship with diseases and tissue regeneration in the mouse liver.Scientific reports · 2023Article
- Epigenome-wide analysis of aging effects on liver regeneration.BMC biology · 2023Article
- Article
- Cell Type-Specific Transcriptional Control of Gsk3β in the Developing Mammalian Neocortex.Frontiers in neuroscience · 2022Article
- Ser9 phosphorylation of GSK-3β promotes aging in the heart through suppression of autophagy.The journal of cardiovascular aging · 2021Article
- Pluripotent Stem Cell-Derived Hepatocytes Phenotypic Screening Reveals Small Molecules Targeting the CDK2/4-C/EBPα/DGAT2 Pathway Preventing ER-Stress Induced Lipid Accumulation.International journal of molecular sciences · 2020Article
- Aging-Related Molecular Pathways in Chronic Cholestatic Conditions.Frontiers in medicine · 2019Review
- Liver regeneration in aged mice: new insights.Aging · 2018Review
- Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.Cell reports · 2018Article
- Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway.Aging cell · 2018Article
- Engineered fibroblast growth factor 19 protects from acetaminophen-induced liver injury and stimulates aged liver regeneration in mice.Cell death & disease · 2017Article
- Inhibition of Glycogen Synthase Kinase 3 Accelerated Liver Regeneration after Acetaminophen-Induced Hepatotoxicity in Mice.The American journal of pathology · 2017Article
- Postponing the Hypoglycemic Response to Partial Hepatectomy Delays Mouse Liver Regeneration.The American journal of pathology · 2016Article
- Potential gene regulatory role for cyclin D3 in muscle cells.Journal of biosciences · 2015Article
- GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway.Acta pharmacologica Sinica · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Aging reduces the regenerative capacities of many tissues. In this paper, we show a critical role of the glycogen synthase kinase 3beta (GSK3beta)-cyclin D3 pathway in the loss of the regenerative capacity of the liver. In young animals, high levels of growth hormone (GH) increase expression of GSK3beta, which associates with cyclin D3 and triggers degradation of cyclin D3. In livers of old mice, the GSK3beta promoter is repressed by C/EBPbeta-histone deacetylase 1 (HDAC1) complexes, leading to the reduction of GSK3beta. The treatment of old mice with GH increases expression of GSK3beta via removal of the C/EBPbeta-HDAC1 complexes from the GSK3beta promoter. We found that the GSK3beta-cyclin D3 pathway is also altered in young GH-deficient Little mice and that treatment of Little mice with GH corrects the GSK3beta-cyclin D3 pathway. We present evidence that GSK3beta regulates liver proliferation by controlling growth-inhibitory activity of C/EBPalpha. The downregulation of GSK3beta in young mice inhibits liver proliferation after partial hepatectomy via the cyclin D3-C/EBPalpha pathway, while the elevation of GSK3beta in old mice accelerates liver proliferation. Thus, this paper shows that GSK3beta is a critical regulator of liver proliferation and that the reduction of GSK3beta with age causes the loss of regenerative capacities of the liver.
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