Prostaglandin D(2) 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. Additionally, 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 to 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.