Association between SPRY1 and TET3 in skin photoaging and natural aging mechanisms

J Cosmet Dermatol. 2024 Apr;23(4):1396-1403. doi: 10.1111/jocd.16115. Epub 2023 Dec 6.

Abstract

Background: SPRY1 is associated with the invasiveness and prognosis of various tumors, and TET3 affects aging by regulating gene expression.

Aims: We investigated the roles of SPRY1 and TET3 in natural skin aging, replicative aging, and photoaging, along with the effect of UVA on genome-wide DNA methylation in HaCaT cells.

Methods: TET3 and SPRY1 expression were measured in the skin of patients of different age groups, as well as in vitro human skin, HaCaT cell replicative senescence, and HaCaT and HaCaT-siTET3 cell photoaging models. Senescence was verified using β-galactosidase staining, and DNA damage was detected using immunofluorescence staining for γ-H2A.X. 5-Methyl cytosine (5-mC) content in the genome was determined using ELISA.

Results: SPRY1 expression increased with age, whereas TET3 expression decreased. Similarly, SPRY1 was upregulated and TET3 was downregulated with increasing cell passages. TET3-siRNA upregulated SPRY1 expression in HaCaT cells. UVA irradiation promoted HaCaT cell senescence and induced cellular DNA damage. SPRY1 was upregulated and TET3 was downregulated upon UVA irradiation. Genome-wide 5-mC content increased upon TET3 silencing and UVA irradiation, indicating a surge in overall methylation.

Conclusions: SPRY1 and TET3 are natural skin aging-related genes that counteract to regulate replicative aging and UVA-induced photoaging in HaCaT cells. The cell photoaging model may limit experimental bias caused by different exposure times of skin model samples.

Keywords: SPRY1; TET3; UVA irradiation; methylation; skin aging.

MeSH terms

  • Cells, Cultured
  • DNA Damage
  • Dioxygenases* / genetics
  • Dioxygenases* / metabolism
  • Dioxygenases* / pharmacology
  • Fibroblasts / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Phosphoproteins / genetics
  • Skin
  • Skin Aging* / genetics
  • Skin Diseases*
  • Ultraviolet Rays / adverse effects

Substances

  • SPRY1 protein, human
  • Membrane Proteins
  • Phosphoproteins
  • TET3 protein, human
  • Dioxygenases