顺铂
纤维化
医学
肾小球硬化
肾
肾脏疾病
养生
病理
药理学
内科学
免疫学
化疗
蛋白尿
作者
Sophia M. Sears,Cierra N. Sharp,Austin Krueger,Gabrielle B. Oropilla,Douglas Saforo,Mark A. Doll,Judit Megyesi,Levi J. Beverly,Leah J. Siskind
出处
期刊:American Journal of Physiology-renal Physiology
[American Physiological Society]
日期:2020-10-01
卷期号:319 (4): F674-F685
被引量:28
标识
DOI:10.1152/ajprenal.00196.2020
摘要
C57BL/6 mice are one of the most commonly used mouse strains in research, especially in kidney injury studies. However, C57BL/6 mice are resistant to chronic kidney disease-associated pathologies, particularly the development of glomerulosclerosis and interstitial fibrosis. Our laboratory and others developed a more clinically relevant dosing regimen of cisplatin (7 mg/kg cisplatin once a week for 4 wk and mice euthanized at day 24) that leads to the development of progressive kidney fibrosis in FVB/n mice. However, we found that treating C57BL/6 mice with this same dosing regimen does not result in kidney fibrosis. In this study, we demonstrated that increasing the dose of cisplatin to 9 mg/kg once a week for 4 wk is sufficient to consistently induce fibrosis in C57BL/6 mice while maintaining animal survival. In addition, we present that cohorts of C57BL/6 mice purchased from Jackson 1 yr apart and mice bred in-house display variability in renal outcomes following repeated low-dose cisplatin treatment. Indepth analyses of this intra-animal variability revealed C-C motif chemokine ligand 2 as a marker of cisplatin-induced kidney injury through correlation studies. In addition, significant immune cell infiltration was observed in the kidney after four doses of 9 mg/kg cisplatin, contrary to what has been previously reported. These results indicate that multiple strains of mice can be used with our repeated low-dose cisplatin model with dose optimization. Results also indicate that littermate control mice should be used with this model to account for population variability.
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