Platelet-rich plasma activates AKT signaling to promote wound healing in a mouse model of radiation-induced skin injury

J Transl Med. 2019 Aug 28;17(1):295. doi: 10.1186/s12967-019-2044-7.

Abstract

Background: The skin is impacted by every form of external radiation therapy. However, effective therapeutic options for severe, acute radiation-induced skin reactions are limited. Although platelet-rich plasma (PRP) is known to improve cutaneous wound healing, its effects in the context of high-dose irradiation are still poorly understood.

Methods: We investigated the regenerative functions of PRP by subjecting the dorsal skin of mice to local irradiation (40 Gy) and exposing HaCaT cells to gamma rays (5 Gy). The cutaneous benefits of PRP were gauged by wound size, histologic features, immunostains, western blot, and transepithelial water loss (TEWL). To assess the molecular effects of PRP on keratinocytes of healing radiation-induced wounds, we evaluated AKT signaling.

Results: Heightened expression of keratin 14 (K14) was documented in irradiated HaCaT cells and skin tissue, although the healing capacity of injured HaCaT cells declined. By applying PRP, this capacity was restored via augmented AKT signaling. In our mouse model, PRP use achieved the following: (1) healing of desquamated skin, acutely injured by radiation; (2) activated AKT signaling, improving migration and proliferation of K14 cells; (3) greater expression of involucrin in keratin 10 cells and sebaceous glands; and (4) reduced TEWL, strengthening the cutaneous barrier function.

Conclusions: Our findings indicate that PRP enhances the functions of K14 cells via AKT signaling, accelerating the regeneration of irradiated skin. These wound-healing benefits may have merit in a clinical setting.

Keywords: Keratin-14; Platelet-rich plasma; Radiation; Regeneration; Skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / radiation effects
  • Disease Models, Animal
  • Humans
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects
  • Keratins / metabolism
  • Mice
  • Platelet-Rich Plasma / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Radiation Injuries / complications*
  • Signal Transduction* / radiation effects
  • Skin / injuries*
  • Skin / pathology
  • Skin / radiation effects
  • Wound Healing* / radiation effects
  • X-Rays

Substances

  • Keratins
  • Proto-Oncogene Proteins c-akt