ArticleThe Journal of clinical investigation1997
Rapamycin (sirolimus) inhibits proliferating cell nuclear antigen expression and blocks cell cycle in the G1 phase in human keratinocyte stem cells.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 76 citations in OpenAlex.
- ML281 Does Not Function as an STK33 Inhibitor but Modulates Proliferation and Differentiation of Keratinocytes Derived from Hypertrophic Scars.International journal of molecular sciences · 2026Article
- From Mechanisms to Management: Tackling In-Stent Restenosis in the Drug-Eluting Stent Era.Current cardiology reports · 2025Review
- Enhancing Fat Graft Survival via Upregulating Autophagy of Adipocytes.Aesthetic plastic surgery · 2024Article
- Sturge-Weber syndrome: updates in translational neurology.Frontiers in neurology · 2024Review
- Curcumin alleviates imiquimod-induced psoriasis-like inflammation and regulates gut microbiota of mice.Immunity, inflammation and disease · 2023Article
- Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures.EMBO reports · 2023Article
- Age-related mechanisms in the context of rheumatic disease.Nature reviews. Rheumatology · 2022Review
- The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling.Frontiers in cell and developmental biology · 2022Review
- Rapamycin and 3-Methyladenine Influence the Apoptosis, Senescence, and Adipogenesis of Human Adipose-Derived Stem Cells by Promoting and Inhibiting Autophagy: An In Vitro and In Vivo Study.Aesthetic plastic surgery · 2021Article
- Metabolic pathways mediate pathogenesis and offer targets for treatment in rheumatic diseases.Current opinion in rheumatology · 2020Review
- mTORC1 loss impairs epidermal adhesion via TGF-β/Rho kinase activation.The Journal of clinical investigation · 2017Article
- The Effect of Dry Eye Disease on Scar Formation in Rabbit Glaucoma Filtration Surgery.International journal of molecular sciences · 2017Article
- A chemical stability study of trimethylsilane plasma nanocoatings for coronary stents.Journal of biomaterials science. Polymer edition · 2017Article
- Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases.Nature reviews. Rheumatology · 2016Review
- Drug Eluting Stents for Malignant Airway Obstruction: A Critical Review of the Literature.Journal of Cancer · 2016Review
- The TRAF-interacting protein (TRAIP) is a novel E2F target with peak expression in mitosis.Oncotarget · 2015Article
- Rhus coriaria induces senescence and autophagic cell death in breast cancer cells through a mechanism involving p38 and ERK1/2 activation.Scientific reports · 2015Article
- [Delayed wound healing during therapy of cutaneous graft-versus-host disease with everolimus].Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2014Article
- Actin filament dynamics impacts keratinocyte stem cell maintenance.EMBO molecular medicine · 2013Article
- Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery.Molecular vision · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Because the immunosuppressant rapamycin (sirolimus) blocks T cell proliferation in G1 phase, it has been proposed as a potential treatment for psoriasis, a skin disease characterized by T cell activation and keratinocyte stem cell hyperproliferation. To determine another potentially important mechanism through which rapamycin can act as an antipsoriatic agent, we tested its direct effect on keratinocyte stem cell proliferation in vitro as well as in vivo. In vivo cell cycle quiescent (G0 phase) stem cell keratinocytes in primary culture sequentially express de novo cyclin D1 and proliferating cell nuclear antigen (PCNA), prior to S phase entry, and upregulate beta1 integrin. Rapamycin inhibited the growth of keratinocytes that were leaving quiescence as well as those already in cell cycle without affecting cell viability. Although beta1 integrin(bright) expression was not affected, the number of beta1 integrin(bright) cells entering S/G2/M was significantly lowered by rapamycin. Cells treated with rapamycin exhibited decreased PCNA expression while cyclin D1 expression, which precedes PCNA expression in the cell cycle, was not affected. We found similar effects on stem cell keratinocytes in patients with psoriasis treated systemically with rapamycin. Because PCNA is required for cell cycle progression from G1 to S phase, our data indicate that inhibition of PCNA protein synthesis may be an important regulatory element in the ability of rapamycin to exert a G1 block.
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