Endogenous N-acyl taurines regulate skin wound healing

Area of Science:

• Biochemistry
• Dermatology
• Lipidomics

Background:

• Fatty acid amide hydrolase (FAAH) is an intracellular enzyme that degrades bioactive lipids.
• N-acyl-taurines (NATs) are lipid-derived molecules, but their physiological roles remain largely unknown.
• FAAH's role in skin physiology and wound repair is not well understood.

Purpose of the Study:

• To investigate the physiological functions of NATs in skin.
• To determine the role of FAAH in skin wound healing.
• To explore the potential of NATs as therapeutic agents for wound repair.

Main Methods:

• Genetic and pharmacological inhibition of FAAH activity in mouse models.
• In vitro studies using human keratinocytes and fibroblasts.
• Untargeted and targeted lipidomics to identify FAAH substrates.
• Administration of synthetic NATs to assess wound healing efficacy.

Main Results:

• Disruption of FAAH accelerated skin wound healing in mice.
• FAAH inhibition stimulated human keratinocyte and fibroblast cell repair processes.
• Two saturated NATs, NAT(24:0) and NAT(20:0), were identified as primary FAAH substrates in mouse skin.
• NAT levels decreased at wound sites and increased during healing.
• Synthetic NAT administration accelerated wound closure and repair responses in vitro and in vivo.
• The mechanism involves epidermal growth factor receptor (EGFR) phosphorylation and calcium signaling, modulated by TRPV1 receptors.

Conclusions:

• FAAH-regulated NAT signaling represents a novel lipid-based mechanism controlling mammalian skin wound healing.
• Targeting FAAH and NATs offers a potential therapeutic strategy for chronic wound treatment.