ArticleArthritis & rheumatology (Hoboken, N.J.)2021
Camptothecin and Topotecan, Inhibitors of Transcription Factor Fli-1 and Topoisomerase, Markedly Ameliorate Lupus Nephritis in (NZB × NZW)F1 Mice and Reduce the Production of Inflammatory Mediators in Human Renal Cells.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases.Biomolecules · 2025Review
- Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth.Nature communications · 2025Article
- FLI1 Induces Plaque Psoriasis and Its Inhibition Attenuates Disease Progression.Journal of inflammation research · 2025Article
- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- FLI-1-driven regulation of endothelial cells in human diseases.Journal of translational medicine · 2024Review
- Topotecan and Ginkgolic Acid Inhibit the Expression and Transport Activity of Human Organic Anion Transporter 3 by Suppressing SUMOylation of the Transporter.Pharmaceutics · 2024Article
- FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression.BMC cancer · 2024Article
- A pharmacological toolkit for human microglia identifies Topoisomerase I inhibitors as immunomodulators for Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy.International journal of molecular sciences · 2024Review
- Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing.Frontiers in immunology · 2024Article
- Increased binding of anti-dsDNA antibodies to short oligonucleotides modified with topoisomerase I reveals a potential new enzyme function independent from DNA relaxation.BMC research notes · 2023Article
- Transcription factor Fli-1 impacts the expression of CXCL13 and regulates immune cell infiltration into the kidney in MRL/lpr mouse.Lupus science & medicine · 2023Article
- Article
- Role of the transcription factor Fli-1 on the CXCL10/CXCR3 Axis.Frontiers in immunology · 2023Article
- Article
- The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease.The Journal of clinical investigation · 2022Article
- DNA Containing Cyclobutane Pyrimidine Dimers Is Released from UVB-Irradiated Keratinocytes in a Caspase-Dependent Manner.The Journal of investigative dermatology · 2022Article
- Topotecan Reduces Neuron Death after Spinal Cord Injury by Suppressing Caspase-1-Dependent Pyroptosis.Molecular neurobiology · 2022Article
- Suppression of Fli-1 protects against pericyte loss and cognitive deficits in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Current insights into the role of Fli-1 in hematopoiesis and malignant transformation.Cellular and molecular life sciences : CMLS · 2022Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveTo examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli-1 and topoisomerase, on lupus nephritis in (NZB × NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on inflammatory mediators in human renal cells.
methodsFemale NZBWF1 mice were treated with vehicle, cyclophosphamide (CYC), CPT (1 mg/kg or 2 mg/kg), or TPT (0.03 mg/kg, 0.1 mg/kg, or 0. 3 mg/kg) by intraperitoneal injection twice a week, beginning at the age of 25 weeks (n = 8-10 mice per group). Blood and urine were collected for monitoring autoantibodies and proteinuria. Mice were euthanized at 40 weeks, and renal pathology scores were assessed. Human renal endothelial and mesangial cells were treated with CPT or TPT, and cytokine expression was measured.
resultsNone of the NZBWF1 mice treated with 1 mg/kg or 2 mg/kg of CPT or 0.3 mg/kg of TPT had proteinuria >100 mg/dl at the age of 40 weeks. One of 8 mice treated with 0.1 mg/kg of TPT and 1 of 10 mice treated with CYC had proteinuria >300 mg/dl, whereas 90% of the mice treated with vehicle had proteinuria >300 mg/dl. Compared to vehicle control, mice treated with 1 mg/kg or 2 mg/kg of CPT, 0.1 mg/kg or 0.3 mg/kg of TPT, or CYC had significantly prolonged survival, attenuated renal injury, diminished splenomegaly, reduced anti-double-stranded DNA autoantibody levels, and reduced IgG and C3 deposits in the glomeruli (all P < 0.05). Human renal cells treated with CPT or TPT had reduced expression of Fli-1 and decreased monocyte chemotactic protein 1 production following stimulation with interferon-α (IFNα) or IFNγ.
conclusionOur findings indicate that low-dose CPT and TPT could be repurposed to treat lupus nephritis.
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