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.
Key Indexing Terms
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Article info
Publication history
Accepted:
October 21,
2015
Received:
May 13,
2015
Footnotes
☆The first four authors (CH, YCH, CCL, SCM) contributed equally.
☆☆The authors have no conflicts of interest to disclose.
☆☆☆All studies were approved by the Institutional Animal Care and Use Committee of Chang Gung Memorial Hospital, Taiwan. This work was supported by Grants (CMRPG6E0021), (CMRPG6D0201), (CMRPG6B0403) and (CMRPG6D0181) from Chang Gung Memorial Hospital, Linkou, Taiwan.
Identification
Copyright
© 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
