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The E3 ubiquitin ligase Itch plays an essential role in kidney fibrosis by inhibiting Dvl2/GSK3β/β-catenin signaling pathway - PubMed

3 hours ago
  • #Dvl2 signaling
  • #kidney fibrosis
  • #E3 ubiquitin ligase
  • Itch, an E3 ubiquitin ligase, shows decreased expression in renal tubules of CKD patients and fibrotic mouse models (UUO and FA).
  • Loss of Itch worsens kidney fibrosis and inflammation, while overexpression alleviates these effects in mice.
  • Itch promotes K48-linked ubiquitination of Dvl2 at lysine 343, leading to its proteasomal degradation.
  • Degradation of Dvl2 suppresses the GSK-3β/β-catenin signaling pathway, reducing fibrotic responses.
  • Itch may serve as a therapeutic target to slow progression of fibrotic kidney disease.