Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production
Abstract via OpenAlex
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.
Evidence snapshot note
This reference is cited by the validated MVA · BUB1B evidence snapshot (data as of 2026-10-17) as Gillespie et al. — rapamycin and normal human fibroblast transcription.
- Model in the source
- 2DD normal human foreskin fibroblasts; two biological replicates per condition
- Where in the publication
- GSE65145 processed tracks; Figures 1 and 3; Figure S2; Cell culture and RNA-seq methods
- Cited by evidence records
- MVA-RAP-GSE65145-001
The note describes how the snapshot used the source; it is not a summary of the publication's conclusions.
Identifiers and provenance
- DOI
10.1080/19491034.2015.1128610- PMID
26652669- PMCID
PMC4915505- Metadata from
- Crossref, Europe PMC, OpenAlex, fetched
- Open access
- Not flagged
- Added
- from the MVA evidence snapshot
In the library
- Collections
- MVA Hackathon 2026 — BUB1B
- Tags
- None yet
- Keywords from the source
- Quiescence, Rapamycin, Rna-seq, Primary Fibroblast, Stat5a/b