Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease.

Abstract

Angiopoietin-like protein 2 (ANGPTL2) stimulates inflammation and is important in the pathogenesis of diabetic kidney disease (DKD). Irbesartan is helpful in reducing diabetes-induced renal damage. In this study, the effects of irbesartan on DKD and its renal protective role involving ANGPTL2 in DKD rats were examined. Wistar rats were divided into normal, DKD, and DKD + irbesartan groups. The DKD + irbesartan group was treated once daily for 8 weeks with 50 mg/kg irbesartan via intragastric gavage. The 24-h urinary albumin was determined each week, renal pathological changes were observed, and expression of ANGPTL2 and nuclear factor-kappa B (NF-κB) in rat renal tissue was assessed by immunohistochemistry. Mouse podocytes cultured in a high concentration of glucose were classified into four groups based on the irbesartan concentrations (0, 25, 50, and 75 ºg/mL). Expression of ANGPTL2 and phosphorylated IκB-α was assessed by Western blotting. The mRNA levels of ANGPTL2 and monocyte chemotactic protein 1 (MCP-1) were assessed by real-time polymerase chain reaction. The DKD rats displayed proteinuria, podocyte injury, and increased ANGPTL2 and NF-κB expression. All were relieved by irbesartan treatment. In podocytes cultured in elevated glucose, ANGPTL2 and phosphorylated IκB-α were overexpressed at the protein level, and ANGPTL2 and MCP-1 were highly expressed at the mRNA level. Irbesartan down-regulated ANGPTL2 and phosphorylated IκB-αexpression at the protein level and inhibited ANGPTL2 and MCP-1 expression at the mRNA level. The ameliorative effects of irbesartan against DKD involves podocyte protection and suppression of ANGPTL2.