12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor.
Bottom Line: Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein-coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4.Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive.These results identify a novel mechanism underlying the action of the 12-HHT/BLT2 axis in epidermal keratinocytes and accordingly suggest the use of BLT2 agonists as therapeutic agents to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.
Affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan Department of Medical Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.Show MeSH
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Mentions: Finally, to address the clinical relevance of our observations, the therapeutic effects of a BLT2 agonist were determined on wound healing in C57BL/6J and db/db mice. The db/db mouse is an animal model of diabetes and exhibits impaired wound closure (Greenhalgh et al., 1990). Topical application of a BLT2 agonist accelerated wound closure by enhancing re-epithelialization in both C57BL/6J mice (Fig. 9, A–E) and db/db mice (Fig. 9, F–J) but not by promoting contraction (Fig. 9, C [middle] and H [middle]), keratinocyte proliferation (Fig. 9, C [bottom] and H [bottom]), or collagen deposition (Fig. 9, E and J). Furthermore, a BLT2 agonist did not influence skin inflammation either (unpublished data). Thus, BLT2 activation in keratinocytes accelerates wound healing by enhancing keratinocyte migration.
Affiliation: Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan Department of Medical Biochemistry, Kyushu University, Fukuoka 812-8582, Japan.