Related Experiment Video

Updated: Feb 27, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

2.0K

The hormetic functions of Wnt pathways in tubular injury

Elisabeth F Gröne1, Giuseppina Federico1, Peter J Nelson2

  • 1Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.

Pflugers Archiv : European Journal of Physiology
|July 8, 2017
PubMed

Insights

Dickkopf 3 (DKK3) drives chronic kidney disease (CKD) progression by promoting fibrosis. Inhibiting DKK3 improved kidney function and reduced fibrosis, highlighting DKK3 as a potential therapeutic target and urinary biomarker for CKD.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Chronic kidney disease (CKD) is characterized by tubulointerstitial damage, tubular atrophy, and fibrosis, which predict disease progression.
  • Wnt signaling pathways are implicated in both the fibrosis of CKD and the regeneration following acute kidney injury.
  • The dual role of Wnt signaling necessitates a deeper understanding of its specific mediators in chronic fibrotic kidney disease.

Purpose of the Study:

  • To investigate the role of Dickkopf 3 (DKK3) in the pathogenesis of chronic kidney disease (CKD).
  • To determine if DKK3 acts as an agonist for Wnt signaling in the context of CKD-associated tubulointerstitial fibrosis.
  • To evaluate the therapeutic potential of inhibiting DKK3 and its utility as a non-invasive biomarker for CKD.

Main Methods:

  • Utilized genetic and antibody-mediated inhibition strategies to block Dickkopf 3 (DKK3) activity in experimental models of CKD.
  • Assessed the impact of DKK3 inhibition on tubular epithelial differentiation and interstitial fibrosis.
  • Analyzed urinary DKK3 levels as a potential non-invasive biomarker for the extent of CKD in human patients.

Main Results:

  • Demonstrated that Dickkopf 3 (DKK3) acts as an agonist for canonical Wnt signaling in chronic kidney disease (CKD).
  • Showed that DKK3 promotes chronic fibrosing inflammation within the tubulointerstitial compartment.
  • Confirmed that genetic and antibody-mediated inhibition of DKK3 significantly improves tubular differentiation and reduces renal fibrosis.
  • Validated urinary DKK3 as a non-invasive biomarker correlating with the extent of CKD in humans.

Conclusions:

  • Dickkopf 3 (DKK3) is a key driver of fibrosing inflammation and tubular atrophy in chronic kidney disease (CKD).
  • Inhibition of DKK3 offers a promising therapeutic strategy for mitigating CKD progression and improving kidney structure.
  • Urinary Dickkopf 3 (DKK3) represents a valuable non-invasive biomarker for assessing CKD severity.
Keywords:
AtrophyDkk3FibrosisWnt pathways

More Related Videos

A Rat Tibial Growth Plate Injury Model to Characterize Repair Mechanisms and Evaluate Growth Plate Regeneration Strategies06:53

A Rat Tibial Growth Plate Injury Model to Characterize Repair Mechanisms and Evaluate Growth Plate Regeneration Strategies

Published on: July 4, 2017

11.7K
Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells06:23

Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells

Published on: November 21, 2025

563

Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.5K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.8K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.5K
Phases of Wound Repair01:28

Phases of Wound Repair

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...
9.1K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.7K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K