Nicousamide blocks the effects of advanced glycation end products on renal cells

Abstract

Advanced glycation end products (AGE) are key factors in the pathogenesis of diabetic nephropathy. AGE can stimulate the expressions of fibrogenic transforming growth factor (TGF-β1) and connective tissue growth factor (CTGF), which in turn induce renal hypertrophy, sclerosis and functional failure. The purpose of this study was to examine nicousamide, a novel coumarin-aspirin derivative, in the treatment of diabetic nephropathy using a renal mesangial and tubular epithelia cell model. RT-PCR and ELISA analyses showed that nicousamide inhibited AGE-induced TGF-β1 and CTGF. Nicousamide blocked AGE-induced G1-arrest in mesangial cells and tubular epithelia by flow cytometry. Suppression of matrix metalloproteinase activity by AGE was restored by nicousamide. This study supports that nicousamide retards diabetic nephropathy by blocking the effects of AGE on renal cells.