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

Objective To investigate the relationship between p38MAPK and COX-2,and to study the role of p38MAPK and COX-2 in pathogenesis of diabetic nephropathy.Methods We initially investigated the protein expression of p38MAPK and the mRNA and protein expressions of COX-2 of rat mesangial cells(cell line HBZy-1) which were incubated with 25 mmol/L glucose,100 nmol/L insulin,100 μmol/L H2O2 and 100 mg/L BSA-AGEs respectively.We also studied the relationship between p38MAPK and COX-2 expressions by using a specific inhibitor(SB203580) of p38MAPK.Results Both p38MAPK and COX-2 had significantly higher expression in rat mesangial cells when incubated with 25 mmol/L glucose,100 nmol/L insulin,100 μmol/L H2O2 and 100 mg/L AGEs,respectively(P0.01),and COX-2 activity was significantly reduced when p38MAPK was inhibited by SB203580(P0.01).Conclusion Both p38MAPK and COX-2 are involved in development of diabetic nephropathy and p38MAPK stimulation is essential for COX-2 expression.