Losartan Protects Podocytes against High Glucose-induced Injury by Inhibiting B7-1 Expression

• 作者: Hui GAO Wen-yan DU Jing LIN Shi-liang HAN Yun-jing ZHANG Xi-feng SUN
• 来源期刊: 当代医学科学（英文）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ORIGINAL ARTICLES
• 页码范围: 505-512
• 页数: 8页
• 语种: 英文
• DOI: 10.1007/s11596-021-2367-5

摘要

The role of B7-1 in podocyte injury has received increasing attention.The aim of this study was to investigate whether losartan protects podocytes of patients with diabetic kidney disease(DKD)by regulating B7-1 and the underlying mechanisms.Rats with streptozotocin-induced DKD were treated with losartan for 8 weeks.Biochemical changes in blood and urine were analyzed.Kidneys were isolated for electron microscopy,immunofluorescence,real-time quantitative PCR(RT-PCR),and Western blot analysis.Immortalized mouse podocyte cells were cultured in normal or high glucose medium in the presence or absence of losartan for 48 h,and then the cells were collected for immunofluorescence,PCR,Western blotting and monolayer permeability detection.The phosphatidylinositol 3-kinase(PI3K)110α subunit and angiotensin Ⅱ type 1 receptor(AT1R)plasmids were transfected into podocytes,respectively,and then Western blotting was performed to assess the expression of B7-1 protein.The results showed that losartan ameliorated podocyte structure and function in the rat model of DKD,and reduced the expression of B7-1 protein.Overexpression of PI3K 110α subunit in podocytes attenuated the inhibitory effect of losartan on B7-1 expression in high glucose-stimulated podocytes.The expression of B7-1 was significantly increased by overexpression of AT1 R and significantly reduced by blocking PI3K 110α subunit.We conclude that losartan protects podocytes against high glucose-induced injury by inhibiting AT1R-mediated B7-1 expression.This effect is dependent on the AT1R-PI3K 110α subunit pathway.