PR002043 (Project)

Description:Frequent injury due to environmental challenges requires constant restoration of the skin barrier. Specific defects in ceramide lipid metabolism have been associated with inflammatory skin diseases such as atopic dermatitis (AD). The goal of this study was to characterize the lipid landscape and biosynthetic pathways activated during epidermal repair using MALDI imaging mass spectrometry (IMS). A keratinocyte culture model of wound healing confirmed that glycerophospholipids and glycosphingolipids are impacted during cell proliferation and that sialic acid supplementation can decrease wound closure time. In skin biopsies of healing tissue taken from healthy volunteers, specific phospholipids were upregulated, including phosphatidylcholine and sphingolipids, which play critical roles in membrane repair and cell signaling. Comparing controls to patients with AD, we again identified defects in ceramide-related lipid metabolism with specific defects in lysophosphatidylcholine (Lyso PC) 18:1. Topical application of LysoPC 18:1 provided modest clinical improvement in a mouse model of AD. We then applied this workflow to samples taken from patients with eczematous phenotypes due to STAT3 dominant negative hyper IgE syndrome and identified metabolic disruption of thiamine and phosphatidylinositol metabolism. Overall, the results indicate MALDI imaging can be used to characterize changes in lipid metabolism during wound healing and may indicate an underappreciated role of LysoPC 18:1 during tissue repair.