PMID- 33263178 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20211204 IS - 2523-899X (Electronic) IS - 2523-899X (Linking) VI - 40 IP - 6 DP - 2020 Dec TI - Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease. PG - 1114-1120 LID - 10.1007/s11596-020-2304-z [doi] AB - 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-kappaB) 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 masculineg/mL). Expression of ANGPTL2 and phosphorylated IkappaB-alpha 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-kappaB expression. All were relieved by irbesartan treatment. In podocytes cultured in elevated glucose, ANGPTL2 and phosphorylated IkappaB-alpha were overexpressed at the protein level, and ANGPTL2 and MCP-1 were highly expressed at the mRNA level. Irbesartan down-regulated ANGPTL2 and phosphorylated IkappaB-alphaexpression 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. FAU - Fang, Ling-Na AU - Fang LN AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. fln_d@sina.com. FAU - Zhong, Shao AU - Zhong S AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. FAU - Huang, Li-Ji AU - Huang LJ AD - Department of Endocrinology and Metabolism, Jiangsu Hospital of Traditional Chinese Medicine, Nanjing, 210029, China. FAU - Lu, Bing AU - Lu B AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. FAU - Shen, Li-Wen AU - Shen LW AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. FAU - Tang, Feng-Yan AU - Tang FY AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. FAU - Sun, He-Ping AU - Sun HP AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. FAU - Zhang, Li AU - Zhang L AD - Department of Endocrinology and Metabolism, Kunshan Hospital Afffiliated to Jiangsu University, Kunshan, Nanjing, 215300, China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20210111 PL - China TA - Curr Med Sci JT - Current medical science JID - 101729993 RN - 0 (Angiopoietin-Like Protein 2) RN - 0 (Angiopoietin-like Proteins) RN - 0 (Angptl2 protein, rat) RN - 0 (NF-kappa B) RN - IY9XDZ35W2 (Glucose) RN - J0E2756Z7N (Irbesartan) SB - IM MH - Angiopoietin-Like Protein 2 MH - Angiopoietin-like Proteins/genetics/*metabolism MH - Animals MH - Cells, Cultured MH - Diabetic Nephropathies/*drug therapy/genetics/metabolism MH - Disease Models, Animal MH - Drug Administration Schedule MH - Glucose/*adverse effects MH - Irbesartan/*administration & dosage/pharmacology MH - Male MH - Mice MH - NF-kappa B/metabolism MH - Phosphorylation/drug effects MH - Podocytes/*cytology/drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Treatment Outcome MH - Up-Regulation/drug effects OTO - NOTNLM OT - angiopoietin-like protein 2 (ANGPTL2) OT - diabetes OT - inflammation OT - kidney EDAT- 2020/12/03 06:00 MHDA- 2021/09/25 06:00 CRDT- 2020/12/02 05:34 PHST- 2020/04/22 00:00 [received] PHST- 2020/10/02 00:00 [accepted] PHST- 2020/12/03 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] PHST- 2020/12/02 05:34 [entrez] AID - 10.1007/s11596-020-2304-z [pii] AID - 10.1007/s11596-020-2304-z [doi] PST - ppublish SO - Curr Med Sci. 2020 Dec;40(6):1114-1120. doi: 10.1007/s11596-020-2304-z. Epub 2021 Jan 11.