title: Targeted metabolic profiling of wounds in diabetic and nondiabetic mice.
abstract: While cellular metabolism is known to regulate a number of key biological processes such as cell growth and proliferation, its role in wound healing is unknown. We hypothesized that cutaneous injury would induce significant metabolic changes and that the impaired wound healing seen in diabetes would be associated with a dysfunctional metabolic response to injury. We used a targeted metabolomics approach to characterize the metabolic profile of uninjured skin and full-thickness wounds at day 7 postinjury in nondiabetic (db/-) and diabetic (db/db) mice. By liquid chromatography mass spectrometry, we identified 129 metabolites among all tissue samples. Principal component analysis demonstrated that uninjured skin and wounds have distinct metabolic profiles and that diabetes alters the metabolic profile of both uninjured skin and wounds. Examining individual metabolites, we identified 62 with a significantly altered response to injury in the diabetic mice, with many of these, including glycine, kynurenate, and OH-phenylpyruvate, implicated in wound healing for the first time. Thus, we report the first comprehensive analysis of wound metabolic profiles, and our results highlight the potential for metabolomics to identify novel biomarkers and therapeutic targets for improved wound healing outcomes.
authors.affiliation: Department of Surgery, Harborview Research & Training Building, University of Washington.
authors.forename: Ravi F
authors.initials: RF
authors.lastname: Sood
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology & Pain Medicine, University of Washington.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Gu
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology & Pain Medicine, University of Washington.
authors.forename: Danijel
authors.initials: D
authors.lastname: Djukovic
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology & Pain Medicine, University of Washington.
authors.forename: Lingli
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Surgery, Harborview Research & Training Building, University of Washington.
authors.forename: Maricar
authors.initials: M
authors.lastname: Ga
authors.affiliation: Department of Surgery, Harborview Research & Training Building, University of Washington.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Muffley
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology & Pain Medicine, University of Washington.|Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Daniel
authors.initials: D
authors.lastname: Raftery
authors.affiliation: Department of Surgery, Harborview Research & Training Building, University of Washington.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hocking
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005260:Female; D055432:Metabolomics / Q000379:methods; D051379:Mice; D058990:Molecular Targeted Therapy; D018919:Neovascularization, Physiologic; D012867:Skin / Q000473:pathology*; D014945:Wound Healing