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Protective or deleterious role of Wnt/beta-catenin signaling in diabetic nephropathy: An unresolved issue

Qiaoyan Guo1, Wei Zhong2, Aosong Duan3

  • 1Department of Nephrology, The Second Hospital of Jilin University, Changchun, 130041, China.

Pharmacological Research
|April 3, 2019
PubMed

Insights

Diabetic nephropathy involves complex Wnt/β-catenin signaling. This pathway can be suppressed, causing kidney damage, or overactivated, leading to podocyte injury and fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Endocrinology

Background:

  • Diabetic nephropathy (DN) is a major complication of diabetes mellitus.
  • The Wnt/β-catenin signaling pathway plays a critical role in kidney development and disease.
  • Dysregulation of Wnt/β-catenin signaling is implicated in the pathogenesis of DN.

Purpose of the Study:

  • To review the dual role of Wnt/β-catenin signaling in diabetic nephropathy.
  • To discuss how Wnt/β-catenin signaling is modulated in DN.
  • To explore therapeutic strategies targeting Wnt/β-catenin signaling in DN.

Main Methods:

  • Literature review of studies investigating Wnt/β-catenin signaling in diabetic nephropathy.
  • Analysis of research on the effects of high glucose and diabetes on Wnt/β-catenin pathway.
  • Examination of pharmacological interventions affecting Wnt/β-catenin signaling in DN.

Main Results:

  • High glucose/diabetes down-regulates Wnt proteins (Wnt4, 5a, 6), decreasing nuclear β-catenin, leading to mesangial cell apoptosis and fibrosis.
  • Suppressed Wnt/β-catenin signaling contributes to detrimental kidney effects in DN.
  • Conversely, diabetes can overactivate Wnt1/β-catenin signaling, causing podocyte injury, epithelial-mesenchymal transition, renal injury, and fibrosis.
  • Pharmacological agents (spironolactone, NO donors, antioxidants) can up-regulate Wnt proteins and activate suppressed signaling, offering benefits in DN.
  • Interventions suppressing overactivated Wnt/β-catenin signaling improve DN symptoms.

Conclusions:

  • Wnt/β-catenin signaling exhibits a dual role in diabetic nephropathy pathogenesis.
  • Understanding this duality is crucial for developing effective therapeutic strategies for DN.
  • Targeting Wnt/β-catenin signaling holds promise for managing diabetic nephropathy.
Keywords:
Beta-CateninDiabetesKidneyNephropathyOxidative stressWnt

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