Endogenous N- Acyl taurines regulate skin wound healing

Oscar Sasso, Silvia Pontis, Andrea Armirotti, Giorgia Cardinali, Daniela Kovacs, Marco Migliore, Maria Summa, Guillermo Moreno-Sanz, Mauro Picardo, Daniele Piomelli

Research output: Contribution to journalArticlepeer-review

Abstract

The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N- Acyl- Taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two longchain saturated NATs-N- Tetracosanoyl- Taurine [NAT(24:0)] and N-eicosanoyl- Taurine [NAT(20:0)]- As primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair- Associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of woundhealing control in mammalian skin, which might be targeted for chronic wound therapy.

Original languageEnglish
Pages (from-to)E4397-E4406
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number30
DOIs
Publication statusPublished - Jul 26 2016

Keywords

  • FAAH
  • FAES
  • Fibroblasts
  • Keratinocytes
  • N- Acyl taurines

ASJC Scopus subject areas

  • General

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