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- Title
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing.
- Authors
Medicherla, Satyanarayana; Wadsworth, Scott; Cullen, Breda; Silcock, Derek; Ma, Jing Y.; Mangadu, Ruban; Kerr, Irene; Chakravarty, Sarvajit; Luedtke, Gregory L.; Dugar, Sundeep; Protter, Andrew A.; Higgins, Linda S.
- Abstract
In healthy tissue, a wound initiates an inflammatory response characterized by the presence of a hematoma, infiltration of inflammatory cells into the wound and, eventually, wound healing. In pathological conditions like diabetes mellitus, wound healing is impaired by the presence of chronic nonresolving inflammation. p38 mitogen-activated protein kinase (MAPK) inhibitors have demonstrated anti-inflammatory effects, primarily by inhibiting the expression of inflammatory cytokines and regulating cellular traffic into wounds. The db/db mouse model of type 2 diabetes was used to characterize the time course of expression of activated p38 during impaired wound healing. The p38α-selective inhibitor, SCIO-469, was applied topically and effects on p38 activation and on wound healing were evaluated. A topical dressing used clinically, Promogran™, was used as a comparator. In this study, we established that p38 is phosphorylated on Days 1 to 7 post-wounding in db/db mice. Further, we demonstrated that SCIO-469, at a dose of 10 μg/wound, had a positive effect on wound contraction, granulation tissue formation, and re-epithelialization, and also increased wound maturity during healing. These effects were similar to or greater than those observed with Promogran™. These results suggest a novel approach to prophylactic and therapeutic management of chronic wounds associated with diabetes or other conditions in which healing is impaired.
- Publication
Diabetes, Metabolic Syndrome & Obesity: Targets & Therapy, 2009, Vol 2, p91
- ISSN
1178-7007
- Publication type
Article