Effects Of Uric Acid On The Expression Of PDZK1, PLXNB2 And ZNF479 In Human Renal Tubular Epithelial Cells

Objective:The present study was to investigate the impact of uric acid(UA) in different concentrations on the expression of gout susceptibility genes(PDZK1, PLXNB2 and ZNF479) in the human renal proximal tubule cell.Methods: Human renal proximal tubule cells(HK-2) were cultured in vitro, and treated with UA of different concentrations(0 mg/dl, 3 mg/dl, 6 mg/dl, and 9 mg/dl) for 48 h. The m RNA of PDZK1, PLXNB2 and ZNF479 were examined by Real-time PCR.Results: There was a significant and positive correlation coefficient between the increased expression of PDZK1 m RNA and the level of UA in HK-2 cells(R=0.847,P=0.01).There was significant difference in the PDZK1 m RNA expression of HK-2 cells among those groups(ANOVA, P=0.001).The expression of PDZK1 m RNA in 9 mg/dl UA group was significantly increased 1.29-fold and 1.21-fold, respectively, compared to the control(P=0.001) and 3 mg/dl UA group(P=0.007). Pearson’s correlation analysis showed a significant positive correlation between UA concentrations and the level of PLXNB2 m RNA in HK-2 cells(R=0.643, P=0.01). There was significant difference in the PLXNB2 m RNA expression of HK-2 cells among those groups(ANOVA, P=0.006).The expression of PLXNB2 m RNA in 9 mg/dl UA group was significantly increased 1.49-fold, 1.66-fold and 1.4-fold, respectively, compared to the control(P=0.02), 3 mg/dl UA group(P=0.005) and 6 mg/dl UA group(P=0.042). Correlation analysis revealed a positive relationship between UA concentrations and the level of ZNF479 m RNA in HK-2 cells(R=0.568, P=0.05). UA induced HK-2 cells to grow elongated morphological shape.Conclusion: UA can up-regulate the expressions of PDZK1, PLXNB2 m RNA and ZNF479 m RNA in human renal proximal tubule cells, and UA can induce human renal proximal tubule fibrosis.