12/15‐ L ipoxygenase deficiency reduces densities of mesenchymal stem cells in the dermis of wounded and unwounded skin

Summary Background Mesenchymal stem cells ( MSC s) promote skin healing. 12/15‐ L ipoxgenase ( 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 ) C57 BL /6 mice. Wounded skin was collected at 3, 8, or 14 days postwounding (dpw). MSC s were analysed in skin sections using histology. 12 S ‐ or 15 S ‐hydroxy‐eicosatetraenoic acid ( HETE ) was analysed using a reversed‐phase C hiral liquid chromatography–ultraviolet–tandem mass spectrometer. Results There were more stem cell antigen ( S ca)1 + CD 29 + MSC s (cells/field) at 3, 8, and 14 dpw, more S ca1 + CD 106 + MSC s at 3 and 14 dpw in the wounded dermis, more MSC s in unwounded dermis of WT mice compared with 12/15‐ LOX −/− mice, and more MSC s in the wounded dermis than in the unwounded dermis. For 12/15‐ LOX −/− dermis, S ca1 + CD 106 + MSC s peaked and S ca1 + CD 29 + MSC s reached a flat level at 8 dpw. However, for the WT dermis, MSC s increased from 8 to 14 dpw. There were more S ca1 + CD 106 + MSC s than S ca1 + CD 29 + MSC s in the 12/15‐ LOX −/− wounded dermis at 8 dpw. However, there were more S ca1 + CD 29 + MSC s in the 12/15‐ LOX −/− than S ca1 + CD 106 + MSC s in the WT wounded dermis at 3 dpw, and S ca1 + CD 106 + MSC s and S ca1 + CD 29 + MSC s were at comparable levels in other conditions. 12/15‐ LOX deficiency suppressed levels of 12/15‐ LOX protein and their products, 12 S ‐ HETE and 15 S ‐ 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.