High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.
Ken DowerShanrong ZhaoFranklin J SchlermanLeigh SavaryGabriela CampanholleBryce G JohnsonLi XiVuong NguyenYutian ZhanMatthew P LechJu WangQing NieMorten A KarsdalFederica GenoveseGermaine BoucherThomas P BrownBaohong ZhangBruce L HomerRobert V MartinezPublished in: PloS one (2017)
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.
Keyphrases
- diabetic nephropathy
- high resolution
- endothelial cells
- type diabetes
- end stage renal disease
- chronic kidney disease
- metabolic syndrome
- cardiovascular disease
- mass spectrometry
- blood pressure
- peritoneal dialysis
- gene expression
- insulin resistance
- weight loss
- cross sectional
- glycemic control
- physical activity
- rna seq
- solid phase extraction
- weight gain
- skeletal muscle
- liquid chromatography
- molecularly imprinted