ArticleAging cell2013
PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a.
Article in Aging cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Single-Cell RNA-seq Analysis Reveals a Positive Correlation between Ferroptosis and Beta-Cell Dedifferentiation in Type 2 Diabetes.Biomedicines · 2024Article
- Understanding cellular senescence: pathways involved, therapeutics and longevity aiding.Cell cycle (Georgetown, Tex.) · 2023Review
- Changes in Pancreatic Senescence Mediate Pancreatic Diseases.International journal of molecular sciences · 2023Review
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
- Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.Frontiers in oncology · 2022Review
- Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR.The American journal of pathology · 2022Article
- Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.Cell reports · 2021Article
- AKT1 Regulates Endoplasmic Reticulum Stress and Mediates the Adaptive Response of Pancreatic β Cells.Molecular and cellular biology · 2020Article
- Regulation of basal expression of hepatic PEPCK and G6Pase by AKT2.The Biochemical journal · 2020Article
- Dual-Specific Protein and Lipid Phosphatase PTEN and Its Biological Functions.Cold Spring Harbor perspectives in medicine · 2020Review
- Long-term c-Kit overexpression in beta cells compromises their function in ageing mice.Diabetologia · 2019Article
- Loss of PTEN induces lung fibrosis via alveolar epithelial cell senescence depending on NF-κB activation.Aging cell · 2019Article
- Targeting p16-induced senescence prevents cigarette smoke-induced emphysema by promoting IGF1/Akt1 signaling in mice.Communications biology · 2019Article
- Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia.Molecular and cellular endocrinology · 2018Article
- PTEN: Tumor Suppressor and Metabolic Regulator.Frontiers in endocrinology · 2018Review
- Nutrient regulation of pancreatic β-cell proliferation.Biochimie · 2017Review
- Conditional abrogation of transforming growth factor-β receptor 1 in PTEN-inactivated endometrium promotes endometrial cancer progression in mice.The Journal of pathology · 2017Article
- Cell Cycle Control by PTEN.Journal of molecular biology · 2017Review
- Crosstalk of LKB1- and PTEN-regulated signals in liver morphogenesis and tumor development.Hepatology communications · 2017Article
- Islet biology, the CDKN2A/B locus and type 2 diabetes risk.Diabetologia · 2016Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue regeneration diminishes with age, concurrent with declining hormone levels including growth factors such as insulin-like growth factor-1 (IGF-1). We investigated the molecular basis for such decline in pancreatic β-cells where loss of proliferation occurs early in age and is proposed to contribute to the pathogenesis of diabetes. We studied the regeneration capacity of β-cells in mouse model where PI3K/AKT pathway downstream of insulin/IGF-1 signaling is upregulated by genetic deletion of Pten (phosphatase and tensin homologue deleted on chromosome 10) specifically in insulin-producing cells. In this model, PTEN loss prevents the decline in proliferation capacity in aged β-cells and restores the ability of aged β-cells to respond to injury-induced regeneration. Using several animal and cell models where we can manipulate PTEN expression, we found that PTEN blocks cell cycle re-entry through a novel pathway leading to an increase in p16(ink4a), a cell cycle inhibitor characterized for its role in cellular senescence/aging. A downregulation in p16(ink4a) occurs when PTEN is lost as a result of cyclin D1 induction and the activation of E2F transcription factors. The activation of E2F transcriptional factors leads to methylation of p16(ink4a) promoter, an event that is mediated by the upregulation of polycomb protein, Ezh2. These analyses establish a novel PTEN/cyclin D1/E2F/Ezh2/p16(ink4a) signaling network responsible for the aging process and provide specific evidence for a molecular paradigm that explain how decline in growth factor signals such as IGF-1 (through PTEN/PI3K signaling) may control regeneration and the lack thereof in aging cells.
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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.