title: Curcumin Rescues Diabetic Renal Fibrosis by Targeting Superoxide-Mediated Wnt Signaling Pathways.
abstract: The purposes of this study were to investigate whether curcumin can weaken diabetic nephropathy by modulating both oxidative stress and renal injury from Wnt signaling mediation. Wnt5a/β-catenin depression and induction of superoxide synthesis are associated with high glucose (HG) induced transforming growth factor (TGF)-β1 and fibronectin expression in mesangial cells. Curcumin resumes HG depression of Wnt/β-catenin signaling and alleviates HG induction of superoxide, TGF-β1 and fibronectin expression in renal mesangial cell. Exogenous curcumin alleviated urinary total proteinuria and serum superoxide level in diabetic rats. Based on laser-captured microdissection for quantitative real-time polymerase chain reaction, it was found that diabetes significantly increased TGF-β1 and fibronectin expression in line with depressed Wnt5a expression. Curcumin treatment reduced the TGF-β1 and fibronectin activation and the inhibiting effect of diabetes on Wnt5a/β-catenin expression in renal glomeruli. Immunohistochemistry showed that curcumin treatment significantly reduced 8-hydroxy-2'-deoxyguanosine, TGF-β1 and fibronectin, and was in line with the restoration of the suppressed Wnt5a expression immunoreactivities in glomeruli of diabetic rats. Curcumin alleviated extracellular matrix accumulation in diabetic nephropathy by not only preventing the diabetes-mediated superoxide synthesis but also resuming downregulation of Wnt/β-catenin signaling. These findings suggest that regulation of Wnt activity by curcumin is a feasible alternative strategy to rescue diabetic renal injury.
authors.affiliation: Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ho
authors.affiliation: Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Yung-Chien
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Chen-Chou
authors.initials: CC
authors.lastname: Lei
authors.affiliation: Department of Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Mau
authors.affiliation: Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Ya-Hsueh
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Department of Nephrology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Tao-Yuan, Taiwan. Electronic address: linchunliang@adm.cgmh.org.tw.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Lin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology
chemical_list: D013481:Superoxides; D003474:Curcumin
keywords: Curcumin; Diabetes; Superoxide; Wnt