Prostaglandin D₂ inhibits wound-induced hair follicle neogenesis through the receptor, Gpr44

Prostaglandins (PGs) are key inflammatory mediators involved in wound healing and regulating hair growth; however, their role in skin regeneration after injury is unknown. Using wound-induced hair follicle neogenesis (WIHN) as a marker of skin regeneration, we hypothesized that PGD 2 decreases follicle neogenesis. PGE 2 and PGD 2 were elevated early and late, respectively, during wound healing. The levels of WIHN, lipocalin-type prostaglandin D 2 synthase (Ptgds), and its product PGD 2 each varied significantly among background strains of mice after wounding, and all correlated such that the highest Ptgds and PGD 2 levels were associated with the lowest amount of regeneration. In addition, an alternatively spliced transcript variant of Ptgds missing exon 3 correlated with high regeneration in mice. Exogenous application of PGD 2 decreased WIHN in wild-type mice, and PGD 2 receptor Gpr44-null mice showed increased WIHN compared with strain-matched control mice. Furthermore, Gpr44-null mice were resistant to PGD 2 -induced inhibition of follicle neogenesis. In all, these findings demonstrate that PGD 2 inhibits hair follicle regeneration through the Gpr44 receptor and imply that inhibition of PGD 2 production or Gpr44 signaling will promote skin regeneration.