Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Invest Dermatol. 2013 Apr;133(4):881-9. doi: 10.1038/jid.2012.398. Epub 2012 Nov 29.
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 PGD2 decreases follicle neogenesis. PGE2 and PGD2 were elevated early and late, respectively, during wound healing. The levels of WIHN, lipocalin-type prostaglandin D2 synthase (Ptgds), and its product PGD2 each varied significantly among background strains of mice after wounding, and all correlated such that the highest Ptgds and PGD2 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 PGD2 decreased WIHN in wild-type mice, and PGD2 receptor Gpr44-null mice showed increased WIHN compared with strain-matched control mice. Furthermore, Gpr44-null mice were resistant to PGD2-induced inhibition of follicle neogenesis. In all, these findings demonstrate that PGD2 inhibits hair follicle regeneration through the Gpr44 receptor and imply that inhibition of PGD2 production or Gpr44 signaling will promote skin regeneration.
前列腺素（PGs）是参与伤口愈合和调节毛发生长的关键炎症介质；然而，它们在受伤后皮肤再生中的作用尚不清楚。我们假设 PGD2 会减少毛囊新生，利用创伤诱导的毛囊新生（WIHN）作为皮肤再生的标志物。在伤口愈合过程中，PGE2 和 PGD2 分别在早期和晚期升高。PGD2 及其产物脂氧素型前列腺素 D2 合酶（Ptgds）的水平在不同背景品系的小鼠中在受伤后均有显著差异，且均呈显著相关，即 Ptgds 和 PGD2 水平最高与再生量最低相关。此外，Ptgds 的一种缺失外显子 3 的选择性剪接转录变体与小鼠的高再生相关。外源性 PGD2 的应用减少了野生型小鼠的 WIHN，而与品系匹配的对照小鼠相比，PGD2 受体 Gpr44 缺失型小鼠的 WIHN 增加。此外，Gpr44 缺失型小鼠对 PGD2 诱导的毛囊新生抑制具有抗性。总之，这些发现表明 PGD2 通过 Gpr44 受体抑制毛囊再生，并暗示抑制 PGD2 产生或 Gpr44 信号将促进皮肤再生。
