Differential chemokine expression in tubular cells in response to urinary proteins from patients with nephrotic syndrome

Abstract

Background and aim: Comparison of urine proteins in idiopathic minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients has been previously conducted, but the relationship between the severity of tubular injury and the composition of urine proteins in various kidney diseases is unknown. This study aimed to investigate the chemokine expression in human tubular cells in response to urine proteins from patients with nephrotic syndrome. Methods: Urine proteins collected from patients with MCD or FSGS were extracted by ultrafiltration and coincubated with HK-2 cells. The expression of the RANTES and MIF genes and the activation of p38 and extracellular regulated kinase were determined. Results: The urine proteins from both MCD and FSGS patients contained a primary band of proteins with Mr of ∼62kDa. The major cytokines present in urine proteins from MCD and FSGS patients were IL-6 and IL-8, while IL-1β, IL-10, IL-12p70 and TNF-α were only detectable. We observed time- and dose-dependent increases in RANTES and MIF expression with urine protein treatment in HK-2 cells. The urine proteins from FSGS patients induced a higher expression of these two chemokines in HK-2 cells compared to the urine proteins from MCD patients. ERK and p38 were activated by urine proteins from either MCD or FSGS patients. Pretreatment with SB203580 or PD98059 abolished the increase in RANTES and MIF expression induced by urine proteins from FSGS patients, while only SB203580 suppressed the high expression induced by urine proteins from MCD patients. Conclusion: These findings indicate that the urine proteins from MCD and FSGS patients induce a differential expression of RANTES and MIF in tubular cells through distinct activation of MAPK-related signaling pathways.