Major enzymatic pathways in dermal wound healing: current understanding and future therapeutic targets.
Skin is an essential protective organ for vertebrate animals. During skin injury, a plethora of cells and mediators occupy the wound site and, through a collective effort, perform repair of the tissue. This complex pathophysiological process is referred to as wound healing. The efficiency of wound repair is governed by the sequential influx of a variety of cell types to the wound site, upregulation/downregulation of many signaling molecules, and the interaction of various enzymatic pathways. Any dysregulation in this highly complex, but orderly, pathophysiological process results in impaired wound repair. A variety of metabolic enzymes are induced upon injury and are responsible for driving the key physiological processes within the wound milieu during the inflammatory and resolution phases of wound repair. This review will focus on the contribution of major enzymatic biosystems to the inflammatory, remodeling and resolution phases of normal wound healing, including the arachidonic acid metabolic pathway, L-arginine metabolism and the endogenous oxidant-antioxidant redox systems of the body. The major therapeutic targets within these processes will also be highlighted.
Kapoor
Mohit
M
Department of Internal Medicine, Rheumatology Division, Kentucky Clinic, University of Kentucky, Lexington, KY 40536-0284, USA. ljcrof2@email.uky.edu
Kojima
Fumiaki
F
Appleton
Ian
I
Kawai
Shinichi
S
Crofford
Leslie J
LJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005609:Free Radicals; D020030:Nitric Oxide Donors; D016718:Arachidonic Acid; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase