Imbalance of Ciliary Programs Drives Fibroblast Differentiation and Fibrotic Signaling in Systemic Sclerosis - PubMed
3 hours ago
- #fibrosis
- #primary cilia
- #systemic sclerosis
- The study explores systemic sclerosis (SSc), a chronic fibrotic disease driven by myofibroblast activation.
- It identifies an imbalance in ciliary programs as a unifying driver of fibrotic activation in SSc.
- Meta-analysis reveals a conserved 15-gene cilia signature altered in SSc across transcriptomic datasets.
- Single-cell trajectory mapping shows SSc fibroblasts have a prolonged 'cilia-off' state, preceding fibrotic gene programs.
- Primary cilia length is significantly reduced in SSc skin and cultured fibroblasts.
- Mechanistically, cilia disruption promotes sustained TGF-β-Hippo signaling, driving fibroblast-to-myofibroblast transition.
- The findings suggest 'ciliotherapy', or stabilizing primary cilia, as a promising antifibrotic strategy for SSc.