12/15-Lipoxygenase deficiency reduces densities of mesenchymal stem cells in the dermis of wounded and unwounded skin

Background Mesenchymal stem cells (MSCs) promote skin healing. 12/15-Lipoxgenase (LOX) is crucial in producing specific lipid mediators in wounded skin. The consequences of 12/15-LOX deficiency in MSC densities in skin are unknown. Objectives To determine the effect of 12/15-LOX deficiency in MSC densities in wounded and unwounded dermis. Methods Full-thickness skin incisional wounds were made to 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT) C57BL/6 mice. Wounded skin was collected at 3, 8, or 14 days postwounding (dpw). MSCs were analysed in skin sections using histology. 12S- or 15S-hydroxy-eicosatetraenoic acid (HETE) was analysed using a reversed-phase Chiral liquid chromatography-ultraviolet-tandem mass spectrometer. Results There were more stem cell antigen (Sca)1(+)CD29(+) MSCs (cells/field) at 3, 8, and 14 dpw, more Sca1(+)CD106(+) MSCs at 3 and 14 dpw in the wounded dermis, more MSCs in unwounded dermis of WT mice compared with 12/15LOX(-/-) mice, and more MSCs in the wounded dermis than in the unwounded dermis. For 12/15-LOX-/- dermis, Sca1(+)CD106(+) MSCs peaked and Sca1(+)CD29(+) MSCs reached a flat level at 8 dpw. However, for the WT dermis, MSCs increased from 8 to 14 dpw. There were more Sca1(+)CD106(+) MSCs than Sca1(+)CD29(+) MSCs in the 12/15-LOX-/- wounded dermis at 8 dpw. However, there were more Sca1(+)CD29(+) MSCs in the 12/15-LOX-/- than Sca1(+)CD106(+) MSCs in the WT wounded dermis at 3 dpw, and Sca1(+)CD106(+) MSCs and Sca1(+)CD29(+) MSCs were at comparable levels in other conditions. 12/15-LOX deficiency suppressed levels of 12/15-LOX protein and their products, 12S-HETE and 15S-HETE, in wounds. Conclusions 12/15-LOX deficiency reduces MSC densities in the dermis, which correlates with the suppressed 12/15-LOX pathways in wounded and unwounded skin.