Advanced glycation end-products (AGEs) induce the production of reactive
oxygen species (ROS) and extra cellular matrix (ECM) degradation via
suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors
(RAGE). This study aimed to reveal whether modulation of NRP-1 by
rosuvastatin (RT) prevents AGE-induced renal injury via targeting
RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats.
Treatment with RT ameliorated the altered level of markers of glycemic
control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA
reductase activity; the level of circulatory carboxymethyl-lysine (CML) and
the accumulation of fluorogenic-AGEs in renal tissue was reduced; the
expression of renal NRP-1, a checkpoint target, was stimulated; the
transcription of RAGE, NF?B-2, TGF-?1 and MMP-2 was suppressed; the
circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was
ameliorated, and renal histopathological features were attenuated as
evidenced by improved glomerular appearance, Bowman?s space and abundant
podocytes in kidneys. In conclusion, RT exhibited the potential to
counteract diabetes and AGE-induced renal pathologies via stimulation of
NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration
(MMP-2) and the inflammatory response (NF?B-2).