ArticlePloS one2013
Inhibition of IGF-1R prevents ionizing radiation-induced primary endothelial cell senescence.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- Murine Model of Radiation Dermatitis with Experimental Wound and Effects of Genistein.International journal of molecular sciences · 2026Article
- Whole-blood RNA biomarkers for predicting survival in non-human primates following thoracic radiation.Scientific reports · 2024Article
- An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.Cellular & molecular biology letters · 2023Review
- Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation.Toxics · 2022Review
- Iron Deposition and Ferroptosis in the Spleen in a Murine Model of Acute Radiation Syndrome.International journal of molecular sciences · 2022Article
- Factors and Pathways Modulating Endothelial Cell Senescence in Vascular Aging.International journal of molecular sciences · 2022Review
- Role of p53 in Regulating Radiation Responses.Life (Basel, Switzerland) · 2022Review
- Cardiovascular ramifications of therapy-induced endothelial cell senescence in cancer survivors.Biochimica et biophysica acta. Molecular basis of disease · 2022Review
- Article
- GH and Senescence: A New Understanding of Adult GH Action.Journal of the Endocrine Society · 2022Review
- Transcriptomic profiling and pathway analysis of cultured human lung microvascular endothelial cells following ionizing radiation exposure.Scientific reports · 2021Article
- Effect of rapamycin on aging and age-related diseases-past and future.GeroScience · 2021Review
- IGF-1 Receptor Signaling Regulates Type II Pneumocyte Senescence and Resulting Macrophage Polarization in Lung Fibrosis.International journal of radiation oncology, biology, physics · 2021Article
- Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence.Pharmacology & therapeutics · 2021Review
- Captopril reduces lung inflammation and accelerated senescence in response to thoracic radiation in mice.Journal of radiation research · 2021Article
- Effect of 3,3'-Diindolylmethane on Pulmonary Injury Following Thoracic Irradiation in CBA Mice.Health physics · 2020Article
- IGF-1 induces cellular senescence in rat articular chondrocytes via Akt pathway activation.Experimental and therapeutic medicine · 2020Article
- Radioprotection and Radiomitigation: From the Bench to Clinical Practice.Biomedicines · 2020Review
- Systems Analysis of Insulin and IGF1 Receptors Networks in Breast Cancer Cells Identifies Commonalities and Divergences in Expression Patterns.Frontiers in endocrinology · 2020Article
- Modeling radiation-induced lung injury: lessons learned from whole thorax irradiation.International journal of radiation biology · 2020Review
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accelerated senescence is a primary response to cellular stresses including DNA damaging agents (e.g., ionizing radiation) and is widely believed to be caused by continuous proliferative signaling in the presence of cell cycle arrest. Studies of signal transduction pathways leading to accelerated senescence have revealed that inhibition of mammalian target of rapamycin (mTOR) by rapamycin rescues cells from senescence. However, the molecular mechanisms upstream of mTOR following ionizing radiation (IR) are not well defined. We investigated signal transduction leading to IR-induced accelerated senescence in human pulmonary artery endothelial cells (HPAEC). Exposure of HPAEC to X-rays (10 Gy, 2.4 Gy/min) upregulated senescence markers including p53, p21/waf1, and senescence-associated beta galactosidase (SA-β-gal). Ly294002 (a phosphatidylinositol-3-kinase [PI3K] inhibitor) or rapamycin (an mTOR inhibitor) blocked the induction of cellular senescence markers suggesting roles for PI3K and mTOR. Pathway-directed microarrays revealed increased transcription of insulin-like growth factor I (IGF-1), a modulator of cell growth and proliferation upstream of mTOR. qRT-PCR confirmed that both IGF-1 and IGF-2 mRNA were increased in response to X-rays, and ELISA showed increased secretion of IGF-1 protein into the medium of irradiated HPAEC. Consistent with upregulation of these ligands, we found that X-ray exposure led to hyperphosphorylation of IGF-1R, the receptor for IGF-1 and -2. Treatment with AG1024, an IGF-1R inhibitor, suppressed IR-induced upregulation of p53, p21/waf1, and SA-β-gal. Together these findings suggest that IGF-1R is a key regulator of IR-induced accelerated senescence in a pathway that requires intact mTOR activity upstream of both p53 and p21/waf1.
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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.