title: 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.
authors.affiliation: Department of pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. lhy2116@gmail.com
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zheng
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000166:cytology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; C526316:CCN2 protein, rat; D003374:Coumarins; D017127:Glycation End Products, Advanced; D061965:Matrix Metalloproteinase Inhibitors; D053773:Transforming Growth Factor beta1; C523324:nicousamide; D055513:Connective Tissue Growth Factor