Azelaic acid reduced senescence-like phenotype in photo-irradiated human dermal fibroblasts: Possible implication of PPARγ

Research output: Contribution to journalArticlepeer-review

Abstract

Azelaic acid (AzA) has been used for the treatment for inflammatory skin diseases, such as acne and rosacea. Interestingly, an improvement in skin texture has been observed after long-time treatment with AzA. We previously unrevealed that anti-inflammatory activity of AzA involves a specific activation of PPARγ, a nuclear receptor that plays a relevant role in inflammation and even in ageing processes. As rosacea has been considered as a photo-aggravated disease, we investigated the ability of AzA to counteract stress-induced premature cell senescence (SIPS). We employed a SIPS model based on single exposure of human dermal fibroblasts (HDFs) to UVA and 8-methoxypsoralen (PUVA), previously reported to activate a senescence-like phenotype, including long-term growth arrest, flattened morphology and increased synthesis of matrix metalloproteinases (MMPs) and senescence-associated β-galactosidase (SA-β-gal). We found that PUVA-treated HDFs grown in the presence of AzA maintained their morphology and reduced MMP-1 release and SA-β-galactosidase-positive cells. Moreover, AzA induced a reduction in ROS generation, an up-modulation of antioxidant enzymes and a decrease in cell membrane lipid damages in PUVA-treated HDFs. Further evidences of AzA anti-senescence effect were repression of p53 and p21, increase in type I pro-collagen and abrogation of the enhanced expression of growth factors, such as HGF and SCF. Interestingly, PUVA-SIPS showed a decreased activation of PPARγ and AzA counteracted this effect, suggesting that AzA effect involves PPARγ modulation. All together these data showed that AzA interferes with PUVA-induced senescence-like phenotype and its ability to activate PPAR-γ provides relevant insights into the anti-senescence mechanism.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalExperimental Dermatology
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Azelaic acid
  • Fibroblasts
  • PPAR-γ
  • PUVA
  • Senescence

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

Fingerprint Dive into the research topics of 'Azelaic acid reduced senescence-like phenotype in photo-irradiated human dermal fibroblasts: Possible implication of PPARγ'. Together they form a unique fingerprint.

Cite this