Inhibition of cyclooxygenase-2 expression contributes to podocyte injury in streptozotocin-induced diabetic rats

Abstract

Objective To investigate the role of cyclooxygenase-2 (COX-2) in podocyte injury in diabetic rats mediated by the disruption of low-density lipoprotein receptor (LDLr) pathway. Methods Eight-week old male Sprague-Dawley (SD) rats were treated for 12 weeks by dividing into three groups: control rats, streptozotocin (STZ) induced diabetic rats (DM), and diabetic rats treated with aspirin (DM+ Aspirin). The plasma lipid profile was checked by clinical biochemistry assay. The ratio of urinary microalbumin to creatinine (ACR) was detected by enzyme-linked immunosorbent assay. Intracellular lipid accumulation was evaluated by Oil Red O staining and a free cholesterol quantitative assay. The glomerular podocyte injury and the expression of molecules related with LDLr pathway were evaluated by electron microscope, immunohistochemical staining, immunofluorescent staining, and Western blotting. Results There were increased levels of urinary ACR (P <0.01) and podocyte injury(P <0.01) in DM rats compared with the controls. Additionally, lipid accumulation in kidneys of DM rats were significantly increased (P <0.01), due to increased protein expressions of COX-2, LDLr, sterol regulatory element-binding protein (SREBP) cleavage activating protein (SCAP), and SREBP-2 (P <0.01). However, these changes were significantly inhibited by an inhibitor of COX-2, Aspirin (P <0.05). It's worth noting that, COX-2 protein expression was closely correlated with LDLr protein expression (r=0.85, P <0.01). Conclusion Dysregulation of LDLr pathway contributes to podocyte injury in diabetic nephropathy, which may be mediated through the increased COX-2 expression. Key words: Cyclooxygenase 2; Receptors, LDL; Diabetic nephropathies; Podocytes