ArticleNucleus (Austin, Tex.)2015
Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production.
Article in Nucleus (Austin, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Fusobacterium nucleatum promotes senescence of human oral mucosa fibroblasts via the Wnt5A/mTOR pathway.Odontology · 2026Article
- Comparative study of adipose tissue derived mesenchymal stem cells with rapamycin on paraquat-induced acute lung injury and pulmonary fibrosis in a mouse model: histological and biochemical study.Stem cell research & therapy · 2025Article
- Article
- Reduction of phosphorylated signal transducer and activator of transcription-5 expression in feline mammary carcinoma.The Journal of veterinary medical science · 2024Article
- Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy.Cancers · 2022Article
- Article
- mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership.International journal of molecular sciences · 2021Review
- Interphase Chromosomes in Replicative Senescence: Chromosome Positioning as a Senescence Biomarker and the Lack of Nuclear Motor-Driven Chromosome Repositioning in Senescent Cells.Frontiers in cell and developmental biology · 2021Article
- Still Living Better through Chemistry: An Update on Caloric Restriction and Caloric Restriction Mimetics as Tools to Promote Health and Lifespan.International journal of molecular sciences · 2020Review
- The Nuclear Lamina: Protein Accumulation and Disease.Biomedicines · 2020Review
- Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts.Scientific reports · 2019Article
- Cytoprotective effects of Avenathramide C against oxidative and inflammatory stress in normal human dermal fibroblasts.Scientific reports · 2019Article
- Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson-Gilford progeria syndrome fibroblasts.Biogerontology · 2018Article
- Rapamycin Inhibits the Growth and Collagen Production of Fibroblasts Derived from Human Urethral Scar Tissue.BioMed research international · 2018Article
- Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan.Frontiers in genetics · 2016Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Rapamycin is a well-known inhibitor of the Target of Rapamycin (TOR) signaling cascade; however, the impact of this drug on global genome function and organization in normal primary cells is poorly understood. To explore this impact, we treated primary human foreskin fibroblasts with rapamycin and observed a decrease in cell proliferation without causing cell death. Upon rapamycin treatment chromosomes 18 and 10 were repositioned to a location similar to that of fibroblasts induced into quiescence by serum reduction. Although similar changes in positioning occurred, comparative transcriptome analyses demonstrated significant divergence in gene expression patterns between rapamycin-treated and quiescence-induced fibroblasts. Rapamycin treatment induced the upregulation of cytokine genes, including those from the Interleukin (IL)-6 signaling network, such as IL-8 and the Leukemia Inhibitory Factor (LIF), while quiescent fibroblasts demonstrated up-regulation of genes involved in the complement and coagulation cascade. In addition, genes significantly up-regulated by rapamycin treatment demonstrated increased promoter occupancy of the transcription factor Signal Transducer and Activator of Transcription 5A/B (STAT5A/B). In summary, we demonstrated that the treatment of fibroblasts with rapamycin decreased proliferation, caused chromosome territory repositioning and induced STAT5A/B-mediated changes in gene expression enriched for cytokines.
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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.