Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease
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40(6):1-7,2020
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Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease* Ling-na FANG1, Shao ZHONG1, Li-ji HUANG2, Bing LU1, Li-wen SHEN1, Feng-yan TANG1, He-ping SUN1, Li ZHANG1 1 Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan 215300, China 2 Department of Endocrinology and Metabolism, Jiangsu Hospital of Traditional Chinese Medicine, Nanjing 210029, China Huazhong University of Science and Technology 2020
Summary: Angiopoietin-like protein 2 (ANGPTL2) stimulates inflammation and is important in the pathogenesis of diabetic kidney disease (DKD). Irbesartan is helpful in reducing diabetesinduced 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 factorkappa 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 µg/mL). Expression of ANGPTL2 and phosphorylated ΙκB-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 ΙκB-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 ΙκB-α expression 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. Key words: angiopoietin-like protein 2 (ANGPTL2); diabetes; kidney; inflammation
As a major diabetic microvascular complication, diabetic kidney disease (DKD) is the main cause of endstage renal disease (ESRD) in western countries and the second leading cause of ESRD in China[1, 2]. DKD affects approximately 30% of patients with diabetes[3]. The main clinical features are proteinuria and renal dysfunction. Proteinuria also contributes significantly to the progression of DKD. Podocytes are a special type of epithelial cells that are important in preserving the integrity of the renal barrier for filtration. Loss or injury of podocytes results in continued progression of proteinuria[4]. Inflammation caused by metabolic disorder and abnormal hemodynamics is associated with DKD progression[5]. Inflammatory cytokines, cell molecules, and chemokines participate in each stage of kidney d
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