A role of sodium selenite in regulating expression of p38 mitogen-activated protein kinase (p38MAPK) and cyclooxygenase-2 (COX-2) in rat mesangial cells

Objective To investigate the relationship between p38 mitogen-activated protein kinase (p38MAPK) and cyclooxygenase-2 (COX-2) and their role in genesis of diabetic nephropathy, and therefore to study the mechanism of sodium selenite in preventing diabetic nephropathy. Methods Initially, expressions of p38MAPK and COX-2 were detected in rat mesangial cell line HBZY-1 which were incubated respectively with 25 mmol/L glucose, 100 nmol/L insulin, 100 μmol/L H2O2 and 100 mg/L AGEs. The relationship between p38MAPK and COX-2 protein expression was investigated by using SB203580, a specific inhibitor of p38MAPK. The direct effects of sodium selenite were then determined on the regulation of p38MAPK and COX-2 protein expression. Results p38MAPK and COX-2 had significantly higher expression in rat mesangial cells line HBZY-1 incubated with 25 mmol/L glucose, 100 nmol/L insulin, 100 μmol/L H2O2 and 100 mg/L AGEs respectively. COX-2 activity was significantly reduced when p38MAPK was inhibited by SB203580. Furthermore, both p38MAPK and COX-2 protein expression were significantly decreased in rat mesangial cell line HBZY-1 with sodium selenite treatment. Conclusions p38MAPK and COX-2 are involved in the development of diabetic nephropathy and p38MAPK stimulation is essential for COX-2 expression, and sodium selenite may play a role in the prevention of diabetic nephropathy by down-regulating both p38MAPK and COX-2 expression.