Objective       To investigate the effect and mechanism of advanced glycation end products (AGEs) on the components of renin-angiotensin system (RAS) in the podoc

ytes.       Methods      Immortalized mouse podocytes were exposed to various concentrations of AGEs for 24 h. The expression levels of renin

angiotensinogen (AGT) and angiotensin Ⅱ type 1 and 2 receptors (AT1R and AT2R)

the level of angiotensin Ⅱ (Ang Ⅱ)

and the activity of angiotensin-converting enzyme (ACE) were assayed. The levels of Akt and phosphorylated Akt were examined by Western blotting. Cell adhesion was measured in the podocytes pretreated with phosphoinositide 3-kinase (PI3-K) inhibitor LY294002

losartan

captopril and chymostatin

respectively.       Results      Treatment with AGEs resulted in significant increase in the expression of AGT and AT1R. Moreover

ACE activity and Ang Ⅱ level increased significantly. However

there was no significant change in renin and AT2R expression. AGEs increased the phosphorylation of Akt by 100%. When the podocytes were pretreated with LY294002 (10 μmol/L)

the AGEs-induced increase in AGT and AT1R expression reduced remarkably. Likewise

ACE activity and Ang Ⅱ level decreased significantly

and the reduced podocyte adhesive capacity induced by AGEs was improved significantly.       Conclusions      AGEs activate the RAS

via

PI3-K/Akt-dependent pathway

and lead to a decrease in podocyte adhesion.