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Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog

Maria Edeling1,2, Grace Ragi1, Shizheng Huang1

  • 1Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 415 Curie Boulevard, 415 Clinical Research Building, Philadelphia, Pennsylvania 19104, USA.

Nature Reviews. Nephrology
|May 4, 2016
PubMed

Insights

Key developmental pathways, Notch, Wnt, and Hedgehog (Hh), are reactivated in kidney injury. Sustained activation of these pathways promotes kidney fibrosis, offering potential therapeutic targets for chronic kidney disease.

Area of Science:

  • Nephrology
  • Developmental Biology
  • Cellular Signaling

Background:

  • Kidney fibrosis is a common sign of kidney disease, characterized by excessive extracellular matrix accumulation.
  • It arises from epithelial injury and inflammation, leading to myofibroblast activation.

Purpose of the Study:

  • To investigate the role of Notch, Wnt, and Hedgehog (Hh) signaling pathways in kidney fibrosis.
  • To explore the potential of targeting these pathways for therapeutic intervention in chronic kidney disease.

Main Methods:

  • Analysis of the reactivation and contribution of Notch, Wnt, and Hh pathways in kidney injury models.
  • Examination of the effects of sustained pathway activation on kidney tissue.

Main Results:

  • Notch, Wnt, and Hh pathways, crucial for embryonic development, are reactivated during kidney injury.
  • Sustained activation of Wnt and Notch inhibits epithelial differentiation.
  • Increased Wnt and Hh signaling drives fibroblast proliferation and myofibroblast differentiation.

Conclusions:

  • The coordinated activation of Notch, Wnt, and Hh pathways plays a critical role in kidney fibrosis development.
  • Inhibiting these pathways presents a promising therapeutic strategy for managing chronic kidney disease fibrosis.

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