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Dickkopf-1 Acts as a Profibrotic Mediator in Progressive Chronic Kidney Disease

Yung-Chien Hsu1,2, Cheng-Chih Chang3, Ching-Chuan Hsieh4

  • 1Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.

International Journal of Molecular Sciences
|April 28, 2023
PubMed

Insights

Elevated Dickkopf-1 (DKK1) levels indicate faster chronic kidney disease (CKD) progression to end-stage renal disease (ESRD). DKK1 acts as a profibrotic mediator in CKD, suggesting it

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Chronic kidney disease (CKD) is a significant global health issue.
  • Wnt/β-catenin signaling plays a critical role in CKD pathogenesis.
  • Variability in CKD progression necessitates identification of predictive markers.

Purpose of the Study:

  • To investigate the role of the Wnt antagonist Dickkopf-1 (DKK1) in CKD progression.
  • To determine if serum DKK1 levels can predict the rate of progression to end-stage renal disease (ESRD).

Main Methods:

  • Serum and renal tissue DKK1 levels were measured in CKD patients (stages 4-5) and controls.
  • An 8-year follow-up study assessed CKD progression in relation to baseline DKK1 levels.
  • A rat model of 5/6 nephrectomy (Nx)-induced CKD was used to evaluate DKK1's role in vivo.
  • DKK1 knockdown was performed in the rat model.
  • Mouse mesangial cells were treated with recombinant DKK1 to assess its effects on fibrogenic protein production.

Main Results:

  • CKD patients (stages 4-5) exhibited higher serum and renal DKK1 levels compared to controls.
  • Higher serum DKK1 levels correlated with faster progression to ESRD in CKD patients.
  • 5/6 Nx rats showed elevated serum and renal DKK1.
  • DKK1 knockdown in 5/6 Nx rats attenuated CKD phenotypes.
  • Recombinant DKK1 induced fibrogenic protein production and endogenous DKK1 expression in mouse mesangial cells.

Conclusions:

  • DKK1 functions as a profibrotic mediator in the context of CKD.
  • Elevated serum DKK1 is a potential independent predictor of accelerated CKD progression to ESRD in advanced stages.
Keywords:
CKDDKK1end-stage renal diseaserenal fibrosisβ-catenin

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