- 【Updated on May 12, 2025】 Integration of CiNii Dissertations and CiNii Books into CiNii Research
- Trial version of CiNii Research Automatic Translation feature is available on CiNii Labs
- Suspension and deletion of data provided by Nikkei BP
- Regarding the recording of “Research Data” and “Evidence Data”
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
-
- Xuan Wang
- Xiangya Hospital Central South University, Changsha, China, and Medical University of South Carolina Charleston
-
- Jim C. Oates
- Medical University of South Carolina and Ralph H. Johnson VA Medical Center Charleston
-
- Kristi L. Helke
- Medical University of South Carolina Charleston
-
- Gary S. Gilkeson
- Medical University of South Carolina and Ralph H. Johnson VA Medical Center Charleston
-
- Xian K. Zhang
- Medical University of South Carolina Charleston
Search this article
Description
<jats:sec><jats:title>Objective</jats:title><jats:p>To 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Female 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>None 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 <jats:italic>P</jats:italic> < 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our findings indicate that low‐dose CPT and TPT could be repurposed to treat lupus nephritis.</jats:p></jats:sec>
Journal
-
- Arthritis & Rheumatology
-
Arthritis & Rheumatology 73 (8), 1478-1488, 2021-06-08
Wiley
- Tweet
Details 詳細情報について
-
- CRID
- 1360861711387058560
-
- ISSN
- 23265205
- 23265191
-
- Data Source
-
- Crossref