p38 MAPK inhibition reduces diabetes-induced impairment of wound healing.

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.

• Authors: Satyanarayana Medicherla, Scott Wadsworth, Breda Cullen, Derek Silcock, Jing Y Ma, Ruban Mangadu, Irene Kerr, Sarvajit Chakravarty, Gregory L Luedtke, Sundeep Dugar, Andrew A Protter, Linda S Higgins
• Journal: Diabetes, metabolic syndrome and obesity : targets and therapy (Diabetes Metab Syndr Obes) Vol. 2 Pg. 91-100 (Jun 23 2009) ISSN: 1178-7007 [Print] New Zealand
• PMID: 21437122 (Publication Type: Journal Article)