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Curcumin Rescues Diabetic Renal Fibrosis by Targeting Superoxide-Mediated Wnt Signaling Pathways
Cheng Ho1, Yung-Chien Hsu2, Chen-Chou Lei2
1Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chiayi, Taiwan.
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.
Insights
Curcumin effectively combats diabetic nephropathy by reducing oxidative stress and restoring Wnt/β-catenin signaling. This natural compound alleviates kidney damage, offering a promising therapeutic strategy for diabetes-related kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Diabetic nephropathy is characterized by oxidative stress and renal injury.
- Wnt signaling pathway dysregulation, specifically Wnt5a/β-catenin depression, is implicated in high glucose-induced kidney damage.
- Transforming growth factor (TGF)-β1 and fibronectin expression are key markers of renal fibrosis in diabetes.
Purpose of the Study:
- To investigate curcumin's potential to mitigate diabetic nephropathy.
- To determine if curcumin modulates oxidative stress and Wnt signaling in diabetic kidney disease.
- To assess curcumin's effect on TGF-β1 and fibronectin expression in renal mesangial cells and glomeruli.
Main Methods:
- In vitro studies using high glucose-induced mesangial cells.
- In vivo studies with diabetic rat models.
- Laser-captured microdissection with quantitative real-time polymerase chain reaction (qRT-PCR).
- Immunohistochemistry to assess oxidative stress markers and protein expression.
Main Results:
- Curcumin reversed high glucose-induced depression of Wnt/β-catenin signaling in mesangial cells.
- Curcumin alleviated high glucose-induced superoxide, TGF-β1, and fibronectin expression.
- In diabetic rats, curcumin reduced proteinuria, serum superoxide levels, and renal TGF-β1 and fibronectin expression.
- Curcumin treatment restored suppressed Wnt5a expression and reduced 8-hydroxy-2'-deoxyguanosine in rat glomeruli.
Conclusions:
- Curcumin mitigates diabetic nephropathy by inhibiting oxidative stress and restoring Wnt/β-catenin signaling.
- Curcumin treatment effectively reduces extracellular matrix accumulation in diabetic kidneys.
- Modulating Wnt activity with curcumin presents a viable therapeutic approach for diabetic renal injury.
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