Increased Smoothened signaling promotes kidney fibrosis through inhibiting autophagy in fibroblasts - PubMed
4 hours ago
- #kidney fibrosis
- #Smo signaling
- #autophagy
- Increased Smoothened (Smo) signaling promotes kidney fibrosis by inhibiting autophagy in fibroblasts.
- Smo upregulation in kidney fibroblasts is linked to chronic kidney disease and diminished autophagy.
- Shh stimulation or ectopic Smo deactivates autophagy, enhancing myofibroblast proliferation and activation.
- Smo activates the β-arrestin 1/Src/β-catenin pathway, inducing mTOR transcription to suppress autophagy.
- Fibroblast-specific knockout of Smo or β-catenin preserves autophagy and reduces kidney fibrosis.
- The Smo antagonist NVP-LDE225 restores fibroblast autophagy and slows fibrotic lesion formation.