p38 MAPK inhibition reduces diabetes-induced impairment of wound healing
Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing Y Ma1, Ruban Mangadu1, Irene Kerr1, Sarvajit Chakravarty1, Gregory L Luedtke1, Sundeep Dugar1, Andrew A Protter1, Linda S Higgins11Scios Inc., Fremont, CA, USA; 2Center for Biomaterials and Advanced Technol...
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2009-06-01
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doaj-d66217c22bda46f580f546002150d7482020-11-24T23:17:13ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity : Targets and Therapy1178-70072009-06-012009default91100p38 MAPK inhibition reduces diabetes-induced impairment of wound healingSatyanarayana MedicherlaScott WadsworthBreda CullenDerek Silcocket al.Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing Y Ma1, Ruban Mangadu1, Irene Kerr1, Sarvajit Chakravarty1, Gregory L Luedtke1, Sundeep Dugar1, Andrew A Protter1, Linda S Higgins11Scios Inc., Fremont, CA, USA; 2Center for Biomaterials and Advanced Technologies, Somerville, NJ, USA; 3Johnson & Johnson Wound Management, Gargrave, UKAbstract: 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, PromogranTM, 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 PromogranTM. 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.Keywords: p38 MAPK ihibition, diabetic wound healing, db/db mouse, nonresolving healing, PromogranTM http://www.dovepress.com/p38-mapk-inhibition-reduces-diabetes-induced-impairment-of-wound-heali-a3283 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Satyanarayana Medicherla Scott Wadsworth Breda Cullen Derek Silcock et al. |
spellingShingle |
Satyanarayana Medicherla Scott Wadsworth Breda Cullen Derek Silcock et al. p38 MAPK inhibition reduces diabetes-induced impairment of wound healing Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy |
author_facet |
Satyanarayana Medicherla Scott Wadsworth Breda Cullen Derek Silcock et al. |
author_sort |
Satyanarayana Medicherla |
title |
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
title_short |
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
title_full |
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
title_fullStr |
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
title_full_unstemmed |
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
title_sort |
p38 mapk inhibition reduces diabetes-induced impairment of wound healing |
publisher |
Dove Medical Press |
series |
Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy |
issn |
1178-7007 |
publishDate |
2009-06-01 |
description |
Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing Y Ma1, Ruban Mangadu1, Irene Kerr1, Sarvajit Chakravarty1, Gregory L Luedtke1, Sundeep Dugar1, Andrew A Protter1, Linda S Higgins11Scios Inc., Fremont, CA, USA; 2Center for Biomaterials and Advanced Technologies, Somerville, NJ, USA; 3Johnson & Johnson Wound Management, Gargrave, UKAbstract: 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, PromogranTM, 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 PromogranTM. 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.Keywords: p38 MAPK ihibition, diabetic wound healing, db/db mouse, nonresolving healing, PromogranTM |
url |
http://www.dovepress.com/p38-mapk-inhibition-reduces-diabetes-induced-impairment-of-wound-heali-a3283 |
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