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ZSF1 fa/faCP大鼠（一种2型糖尿病肾病模型）肾脏疾病进展的高分辨率分子和组织学分析

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

作者信息

Dower Ken, Zhao Shanrong, Schlerman Franklin J, Savary Leigh, Campanholle Gabriela, Johnson Bryce G, Xi Li, Nguyen Vuong, Zhan Yutian, Lech Matthew P, Wang Ju, Nie Qing, Karsdal Morten A, Genovese Federica, Boucher Germaine, Brown Thomas P, Zhang Baohong, Homer Bruce L, Martinez Robert V

机构信息

Inflammation and Immunology, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, United States of America.

Clinical Bioinformatics, Early Clinical Development, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, United States of America.

出版信息

PLoS One. 2017 Jul 26;12(7):e0181861. doi: 10.1371/journal.pone.0181861. eCollection 2017.

DOI:10.1371/journal.pone.0181861
PMID:28746409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5529026/
Abstract

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

摘要

ZSF1大鼠表现出继发于肥胖、高血压和糖尿病的自发性肾病，作为一种对人类进行性疾病具有潜在高转化价值的模型系统而受到关注。为了全面表征该模型，并更好地了解它与人类疾病的相似程度，我们对ZSF1大鼠从早期疾病到终末期肾病的肾脏疾病进展进行了高分辨率纵向分析。分析包括代谢终点、肾脏组织学和超微结构、纤维化尿生物标志物的评估以及疾病过程中肾小球富集组织的转录组分析。我们的研究结果支持ZSF1大鼠模型的转化价值，在此提供这些结果以帮助研究人员确定该模型是否适合测试特定的感兴趣机制、设计治疗干预研究以及识别2型糖尿病肾病的新靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbcd/5529026/f306759532ba/pone.0181861.g008.jpg
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