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Updated: Jun 17, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction

Chun-Liang Lin1, Jeng-Yi Wang, Jih-Yang Ko

  • 1Department of Nephrology, Chang Gung Memorial Hospital, Chiayi,Taiwan.

Journal of the American Society of Nephrology : JASN
|December 19, 2009
PubMed

Insights

Dickkopf-1 (DKK-1) drives kidney damage in diabetic nephropathy by disrupting beta-catenin signaling. Inhibiting DKK-1 protected against high glucose-induced fibrosis and improved kidney function in diabetic rats.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Endocrinology

Background:

  • Wnt/beta-catenin signaling is implicated in renal fibrosis, including diabetic nephropathy.
  • Dickkopf-1 (DKK-1), an endogenous Wnt inhibitor, has an unknown role in diabetic kidney disease.

Purpose of the Study:

  • To investigate DKK-1's role in high glucose-induced profibrotic factor expression and renal damage.
  • To determine if DKK-1 inhibition could be a therapeutic strategy for diabetic nephropathy.

Main Methods:

  • In vitro studies using mesangial cells exposed to high glucose.
  • In vivo studies using streptozotocin-induced diabetic rats with DKK-1 modulation.
  • Assessed expression of fibrotic markers, beta-catenin signaling, and kidney microstructure.

Main Results:

  • High glucose increased DKK-1, Kremen-2, TGF-beta1, and fibronectin in mesangial cells.
  • DKK-1 modulated high glucose-induced c-Jun, TGF-beta1, and fibronectin expression, and affected beta-catenin phosphorylation.
  • DKK-1 knockdown in diabetic rats reduced proteinuria, mesangial matrix, and glomerular volume.

Conclusions:

  • DKK-1 mediates high glucose-induced beta-catenin destabilization and matrix accumulation in mesangial cells.
  • DKK-1 inhibition ameliorates diabetes-induced renal dysfunction and microstructural damage.
  • Targeting DKK-1 presents a potential therapeutic avenue for diabetic nephropathy.

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