After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration

Area of Science:

• Regenerative Medicine
• Developmental Biology
• Immunology

Background:

• Large wounds in adult mammals can induce new hair follicle formation (wound-induced hair neogenesis, WIHN).
• Prostaglandin E2 (PGE2) is crucial for regeneration and activates the Wnt/β-catenin pathway, which regulates WIHN.
• Noncoding double-stranded RNA (dsRNA) released during wounding stimulates WIHN via toll-like receptor 3.

Purpose of the Study:

• To investigate if dsRNA induces the β-catenin pathway through prostaglandin E2.
• To elucidate the role of dsRNA in controlling prostaglandin and Wnt signaling during skin regeneration.

Main Methods:

• In vivo analysis of WIHN levels and Wnt7b production in mice.
• Assessment of dsRNA's effect on Wnt7b induction, requiring Ptgs2 (prostaglandin-endoperoxide synthase 2).
• Use of the Ptgs2 inhibitor celecoxib and exogenous prostaglandin E2 to modulate WIHN and Wnt7b.

Main Results:

• WIHN levels strongly correlated with Wnt7b production.
• dsRNA induced Wnt7b production in a Ptgs2-dependent manner.
• Celecoxib treatment reduced dsRNA-induced WIHN and Wnt7b; exogenous PGE2 rescued these effects.

Conclusions:

• Noncoding dsRNA acts upstream to coordinate prostaglandin and Wnt signaling in skin regeneration.
• This study highlights dsRNA as a critical initiator of WIHN, involving the PGE2 and Wnt/β-catenin pathways.
• Findings offer insights into the molecular mechanisms controlling hair follicle regeneration after injury.