title: 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: Scios Inc., Fremont, CA, USA.
authors: Satyanarayana
authors: S
authors: Medicherla
authors: Scott
authors: S
authors: Wadsworth
authors: Breda
authors: B
authors: Cullen
authors: Derek
authors: D
authors: Silcock
authors: Jing Y
authors: JY
authors: Ma
authors: Ruban
authors: R
authors: Mangadu
authors: Irene
authors: I
authors: Kerr
authors: Sarvajit
authors: S
authors: Chakravarty
authors: Gregory L
authors: GL
authors: Luedtke
authors: Sundeep
authors: S
authors: Dugar
authors: Andrew A
authors: AA
authors: Protter
authors: Linda S
authors: LS
authors: Higgins