Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat model

Abstract

BackgroundIn contrast to blood, which has mechanisms to maintain a homeostatic internal environment, urine is more likely to reflect changes in the body. As urine accumulates all types of changes, identifying the precise cause of changes in the urine proteome is challenging and crucial in biomarker discovery. To reduce the effects of both genetic and environmental factors on the urinary proteome, this study used a rat model of adriamycin-induced nephropathy resembling human focal segmental glomerulosclerosis (FSGS) development.ResultsUrine samples were collected at before adriamycin administration and day3, 7, 11, 15 and 23 after. Urinary proteins were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Of 23 changed proteins with disease development, 20 have human orthologs, and 13 proteins were identified as stable in normal human urine, meaning that changes in these proteins are more likely to reflect disease. Fifteen of the identified proteins have not been established to function in FSGS development. Seven proteins were selected for verification in ten more rats as markers closely associated with disease severity by western blot.ConclusionWe identified proteins changed in different stages of FSGS in rat models, which may aid in biomarker development and the understanding of FSGS pathogenesis.

Urine Proteome Changes in a TNBS‐Induced Colitis Rat Model

“…From the histopathology investigations, the second day of TNBS‐induced colitis displayed mainly acute intestinal mucosal injury due to the effect of ethanol in the enema. The histopathological characteristics of the TNBS‐7 day group resemble features of human immune inflammatory bowel disease (Crohn's disease) . Therefore, nine proteins showing differential abundance in the TNBS‐7 day group have the potential to be urinary biomarkers of inflammatory bowel disease.…”

“…Candidate biomarkers of many diseases have been identified in urine using animal models. For example, significant changes in urine occurred in a unilateral ureteral obstruction rat model, and urinary proteins showed continuous changes with disease progression in an adriamycin‐induced focal segmental glomerulosclerosis model . The urinary proteome changed significantly before clinical symptoms and histopathological changes occurred in a bleomycin‐induced pulmonary fibrosis model, an experimental autoimmune myocarditis model, a bacterial meningitis rat model, a glioblastoma animal model, and a Walker‐256 tumor‐bearing rat model …”

Early urine proteome changes in an implanted bone cancer rat model

“…The urinary proteins changed significantly in the renal interstitial fibrosis model constructed by unilateral ureteral ligation [6]. In the model of focal segmental glomerulosclerosis induced by doxorubicin, the urinary proteins were continuously changing with disease progression [7]. There are other models of organ diseases as follows: bleomycin-induced pulmonary fibrosis model [8], experimental autoimmune myocarditis model [9], rat model of bacterial meningitis [10], glioblastoma animal model [11], tumor model of the subcutaneous implantation of Walker 256 cells [12], rat model of chronic pancreatitis induced by diethyldithiocarbamate [13], rat model of NuTu-19 lung metastasis [14], Walker 256 intracerebral tumor model [15], and Walker 256 lung metastasis rat model [16].…”

Urinary protein changes in the early phase of smoking-induced Chronic Obstructive Pulmonary Disease in a rat model

“…Compared with blood, urine lacks mechanisms for maintaining homeostasis and therefore accumulates 40 changes from the body. Through the proteomic analysis of myocarditis [7], glomerulosclerosis [8], ureteral obstruction [9], bacterial meningitis[10], diabetes [11], pulmonary fibrosis [12], subcutaneous tumors [13], and glioblastoma [14] in rat urine, it was found that urine protein can reflect the early changes in various diseases with clinical application prospects.…”