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Updated: Feb 7, 2026

Development of Human Renal Tubular Epithelial Cell Primary Cultures in Monolayers and Three-Dimensional Conditions
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Published on: June 13, 2025

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Getting a Notch closer to renal dysfunction: activated Notch suppresses expression of the adaptor protein Disabled-2

Katharina Schütte-Nütgen1, Maria Edeling1, Gudrun Mendl1

  • 1Internal Medicine D, University Hospital Muenster, Muenster, Germany; and.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|July 28, 2018
PubMed

Insights

Activated Notch signaling in kidney disease suppresses Disabled-2 (Dab2) expression, a crucial protein for renal function. Loss of Dab2 impairs kidney filtration and exacerbates injury, highlighting its protective role in chronic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Notch signaling reactivation is implicated in chronic kidney disease (CKD) pathogenesis, contributing to renal epithelial injury and fibrosis.
  • The precise mechanisms by which Notch signaling drives kidney dysfunction remain incompletely understood.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying Notch-induced injury in renal epithelial cells.
  • To identify key Notch target genes involved in kidney disease progression.

Main Methods:

  • Genome-wide transcriptome analysis of cultured tubular epithelial cells expressing activated Notch1.
  • Utilized Drosophila nephrocytes to study the functional role of the Drosophila homolog of Dab2 (Dab).
  • Assessed Dab2 expression's role in endocytic regulation and protection against TGF-β-induced epithelial-to-mesenchymal transition in vitro.
  • Conducted in vivo studies to correlate Dab2 expression with renal ischemia-induced injury.

Main Results:

  • Activated Notch signaling significantly downregulated the expression of Disabled-2 (Dab2) in tubular epithelial cells.
  • Knockdown of Drosophila Dab resulted in significant kidney filtration defects.
  • Dab2 expression is critical for endocytic regulation and confers protection against TGF-β-induced epithelial-to-mesenchymal transition.
  • Dab2 plays a role in mitigating renal ischemia-induced injury in vivo.

Conclusions:

  • Activated Notch signaling suppresses Dab2 expression in renal tubular epithelial cells, contributing to kidney dysfunction.
  • Dab2 is a versatile protein with essential roles in kidney filtration, endocytic regulation, and protection against injury.
  • Targeting Dab2 may offer a therapeutic strategy for both acute and chronic kidney diseases.
Keywords:
Dab2NICD1endocytosiskidney function

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