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. Wnt 5a/β-catenin depression and induction of superoxide synthesis are associated
with high glucose (HG)–induced transforming growth factor beta 1 (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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References
- Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients.Diabetes. 1989; 38: 1077-1081
- WNT/β-catenin signaling regulates multiple steps of myogenesis by regulating step-specific targets.Mol Cell Biol. 2015; 35: 1763-1776
- Wnt/catenin signaling in adult stem cell physiology and disease.Stem Cell Rev. 2014; 10: 512-525
- Superoxide destabilization of beta-catenin augments apoptosis of high-glucose-stressed mesangial cells.Endocrinology. 2008; 149: 2934-2942
- Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells.J Am Soc Nephrol. 2006; 17: 2812-2820
- Simvastatin reverses high glucose-induced apoptosis of mesangial cells via modulation of Wnt signaling pathway.Am J Nephrol. 2008; 28: 290-297
- Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction.J Am Soc Nephrol. 2010; 21: 124-135
- Sustained Wnt/β-catenin signaling rescues high glucose induction of transforming growth factor-β1-mediated renal fibrosis.Am J Med Sci. 2012; 344: 374-382
- Multitargeting by curcumin as revealed by molecular interaction studies.Nat Prod Rep. 2011; 28: 1937-1955
- The targets of curcumin.Curr Drug Targets. 2011; 12: 332-347
- Safety and anti-inflammatory activity of curcumin: a component of turmeric (Curcuma longa).J Altern Complement Med. 2003; 9: 161-168
- Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice.J Agric Food Chem. 2005; 53: 959-963
- Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials.Antioxid Redox Signal. 2008; 10: 511-545
- Curcumin the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.Clin Exp Pharmacol Physiol. 2006; 33: 940-945
- Change in post-translational modifications of histone H3, heat-shock protein-27 and MAP kinase p38 expression by curcumin in streptozotocin-induced type I diabetic nephropathy.Br J Pharmacol. 2008; 153: 1225-1231
- Ras modulation of superoxide activates ERK-dependent fibronectin expression in diabetes-induced renal injuries.Kidney Int. 2006; 69: 1593-1600
- Nitric oxide donors rescue diabetic nephropathy through oxidative-stress-and nitrosative-stress-mediated Wnt signaling pathways.J Diabetes Investig. 2015; 6: 24-34
- Benefits from dietary polyphenols for brain aging and Alzheimer’s disease.Neurochem Res. 2008; 33: 2390-2400
- Curcumin: the Indian solid gold.Adv Exp Med Biol. 2007; 595: 1-75
- Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3.Anticancer Res. 2006; 26: 4379-4389
- WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers.Exp Neurol. 2015; 264: 14-25
- Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling.Am J Physiol Cell Physiol. 2010; 298: C1510-C1516
- Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPs we transfected SY5Y cells.Eur J Pharm Sci. 2011; 42: 540-546
- Potent growth suppressive activity of curcumin in human breast cancer cells: modulation of Wnt/beta-catenin signaling.Chem Biol Interact. 2009; 181: 263-271
- Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells.Eur J Pharm Sci. 2011; 42: 540-546
Article info
Publication history
Published online: March 24, 2016
Publication stage
In Press Journal Pre-ProofFootnotes
☆All studies were approved by the Institutional Animal Care and Use Committee of Chang Gung Memorial Hospital, Taiwan. This work was supported by grant [CMRPG6E0021], grant [CMRPG6D0201], grant [CMRPG6B0403] and grant [CMRPG6D0181] from Chang Gung Memorial Hospital, Taiwan.
☆☆The authors declare that there are no conflicts of interest.
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© 2016 Published by Elsevier Inc.
