Role of renin-angiotensin system in advanced glycation end products-induced changes of permeability in rat glomerular endothelial cells / 中华肾脏病杂志

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.