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Topical Docosahexaenoic Acid (DHA) Accelerates Skin Wound Healing in Rats and Activates GPR120

Background: The development of methods for improving skin wound healing may have an impact on the outcomes of a number of medical conditions. The topical use of polyunsaturated fatty acids (PUFAs) can accelerate skin wound healing through mechanisms that involve, at least in part, the modulation of inflammatory activity. Purpose: We evaluated whether G-protein-coupled receptor 120 (GPR120), a recently identified receptor for docosahexaenoic acid (DHA) with anti-inflammatory activity, is expressed in the skin and responds to topical DHA. Method: Male Wistar rats were submitted to an 8.0-mm wound on the back and were immediately administered a topical treatment of a solution containing 30 μM of DHA once a day. The healing process was photodocumented, and tissues were collected on Days 5, 9, and 15 for protein and RNA analyses and histological evaluation. Results: GPR120 was expressed in the intact skin and in the wound. Keratinocytes expressed the most skin GPR120, while virtually no expression was detected in fibroblasts. Upon DHA topical treatment, wound healing was significantly accelerated and was accompanied by the molecular activation of GPR120, as determined by its association with β-arrestin-2. In addition, DHA promoted a reduction in the expression of interleukin (IL) 1β and an increase in the expression of IL-6. Furthermore, there was a significant increase in expression of transforming growth factor β (TGF-β) and the keratinocyte marker involucrin. Discussion: Topical DHA improved skin wound healing. The activation of GPR120 is potentially involved in this process.