Role of renin-angiotensin system in advanced glycation end products-induced changes of permeability in rat glomerular endothelial cells
10.3760/cma.j.issn.1001-7097.2011.09.009
- VernacularTitle:肾素血管紧张素系统在晚期糖基化终产物改变肾小球内皮细胞通透性中的作用
- Author:
Canming LI
;
Zengchun YE
;
Hui PENG
;
Pengli LUO
;
Weiyan LAI
;
Ming LI
;
Tanqi LOU
- Publication Type:Journal Article
- Keywords:
Glycosylation end products,advanced;
Renin-angiotensin system;
Permeability;
Glomerular endothelial cells;
Tight junction
- From:
Chinese Journal of Nephrology
2011;27(9):667-672
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of advanced glycation end products (AGEs) on the disruption of tight junctions in rat glomerular endothelial cells (rGEnCs) and the role of renin-angiotensin system (RAS) in this pathological procedure.Methods Primary cultured rGEnCs were incubated with AGEs at concentrations of 20 mg/L,40 mg/L and 80 mg/L,for 6 h,12 h and 24 h respectively.The cells were treated with captopril (1 mmol/L) or valsartan (10 μ mol/L)to block RAS.The endothelial permeability was investigated by transendothelial electrical resistance and the flux of fluorescein isothiocyanate-conjugated bovine serum albumin.The expression of AGEs receptor (RAGE),tight junction proteins [occludin,claudin-5,junctional adhesion molecules A (JAM-A) and zona occludens-1 (ZO-1)]and RAS components [angiotensinogen,renin and angiotensin Ⅱ type 1 receptor (AT1)]were detected by Western blotting.Immunofluorescence was used to demonstrate the disruptions of the tight junction proteins.The activity of angiotensin converting enzyme (ACE) was evaluated by UV spectrophotometry.Angiotensin Ⅱ (Ang Ⅱ ) was measured by enzyme immunoassay.Results The monolayer permeability,the expression of RAGE,the activity of ACE,the concentration of Ang Ⅱ and the expression of AT1 of rGEnCs were increased after induced by AGEs.Meanwhile,AGEs decreased the expression of occludin,claudin5 and JAM-A and induced disruption of tight junction proteins.Pretreatment with anti-RAGE antibody (100 mg/L),captopril or valsartan could attenuate the detrimental effect of AGEs.Conclusion The changes of permeability induced by AGEs in glomerular endothelial cells are partly mediated by RAS through RAGE.