15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth

Naunyn Schmiedebergs Arch Pharmacol. 2016 Jul;389(7):809-13. doi: 10.1007/s00210-016-1257-z. Epub 2016 May 17.

Abstract

Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.

Keywords: 15-dPGJ2; Apoptosis; DP2; Follicular keratinocytes; Hair loss; PGD2.

MeSH terms

  • Alopecia / metabolism
  • Alopecia / pathology
  • Alopecia / physiopathology
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Hair / growth & development
  • Hair / metabolism
  • Hair Follicle / drug effects*
  • Hair Follicle / pathology
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / pathology
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / toxicity
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / metabolism

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Prostaglandin D2
  • prostaglandin D2 receptor