Project description:Characterization of the transcriptional signatures of 771 human genes and 19 coronavirus genes in skin samples collected from the borders of hospital-acquired sacral pressure injuries (HASPIs) that developed in individuals with and without COVID-19. Samples included pressure ulcers from individuals without COVID-19 (10), pressure ulcers from individuals with COVID-19 (5), as well as pressure ulcers with thrombotic vasculopathy histopathology from individuals with COVID-19 (8).
Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.
