Effects of low-dose ALA-PDT on fibroblast photoaging induced by UVA irradiation and the underlying mechanisms

Photodiagnosis Photodyn Ther. 2019 Sep:27:79-84. doi: 10.1016/j.pdpdt.2019.05.006. Epub 2019 May 7.

Abstract

Objectives: To investigate the effects of low-dose aminolevulinic acid photodynamic therapy (ALA-PDT) on photoaging in human dermal fibroblasts (HDFs) and to explore the mechanism of Nuclear factor erythroid 2-related factor 2(Nrf2)-mediated photorejuvenation in vitro.

Methods: A photoaging model was established through repeated exposure of HDFs to UVA. Total superoxide dismutase (SOD) expression was detected by a SOD activity assay. Nrf2 was knocked down through adenovirus infection, and successful knockdown was confirmed by Western blot analysis and quantitative polymerase chain reaction.

Results: Sustained exposure to UVA induced photoaging in HDFs. Total SOD activity was significantly increased by low-dose aminolevulinic acid (ALA)-PDT. Upon application of low doses of ALA-PDT to photoaging HDFs, Nrf2 was translocated to the nucleus; in addition, the expression of Nrf2, transforming growth factor-β1 (TGF-β1), type I and III collagen (COL1 and COL3), heme oxygenase 1 (HO-1), and p-ERK was increased, while the expression of matrix metalloproteinase 9 (MMP-9) was decreased. However, after Nrf2 was knocked down in HDFs, the expression of TGF-β1, COL1, COL3, and HO-1 was significantly decreased, while the expression of MMP-9 was increased.

Conclusion: This study revealed that low-dose ALA-PDT decreases UVA-mediated photoaging through an Nrf2-mediated antioxidant effect.

Keywords: ALA-PDT; HDFs; NF-E2-related factor 2 (Nrf2); Photoaging.

MeSH terms

  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / pharmacology*
  • Collagen / metabolism
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects*
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Nuclear Respiratory Factors / metabolism
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacology*
  • Random Allocation
  • Skin Aging / drug effects*
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Ultraviolet Rays

Substances

  • Nuclear Respiratory Factors
  • Photosensitizing Agents
  • Transforming Growth Factor beta1
  • Aminolevulinic Acid
  • Collagen
  • Heme Oxygenase-1
  • Superoxide Dismutase