Proteomic analysis indicates altered expression of plasma proteins in a rat nephropathy model

Abstract

Minimal-change nephrotic syndrome is an idiopathic disease in which protein leaks through podocytes into the urine. We used proteomic tools to examine differences of plasma protein expression in healthy rats and rats with doxorubicin-induced nephropathy treated with or without prednisone. Healthy three-month-old Sprague-Dawley male rats were randomly chosen for one injection of doxorubicin (5.5 mg/kg) through the caudal vein to induce nephropathy (n = 50) or the same volume of saline (control, n = 20). After 1 week, 25 rats in the nephropathy group received topical prednisone (5.5 mg/kg/day) for 21 days and another 25 rats (untreated nephropathy) and the control rats received topical water. At 4 weeks, protein chips generated from rat plasma samples were analyzed by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS) to obtain mass-to-charge ratios (m/z) of proteins of 2-50 kDa. Relative to control rats, untreated nephropathic rats had four significantly higher and seven significantly lower m/z peaks. Prednisone treatment significantly normalized the intensities of peaks 9069 and 15005 (which correspond to cortexin-1 and interleukin-17A, respectively, according to Swiss Prot database) by increasing the expression of 9069 but reducing expression of 15005. Significant differences in plasma proteins can be identified by proteomic analysis using SELDI-TOF-MS in a rat model of nephropathy.