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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2009-06-01
|
Series: | Diabetes, Metabolic Syndrome and Obesity |
Online Access: | http://www.dovepress.com/p38-mapk-inhibition-reduces-diabetes-induced-impairment-of-wound-heali-a3283 |
_version_ | 1811173830304989184 |
---|---|
author | Satyanarayana Medicherla Scott Wadsworth Breda Cullen Derek Silcock et al. |
author_facet | Satyanarayana Medicherla Scott Wadsworth Breda Cullen Derek Silcock et al. |
author_sort | Satyanarayana Medicherla |
collection | DOAJ |
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 |
first_indexed | 2024-04-10T17:54:29Z |
format | Article |
id | doaj.art-d66217c22bda46f580f546002150d748 |
institution | Directory Open Access Journal |
issn | 1178-7007 |
language | English |
last_indexed | 2024-04-10T17:54:29Z |
publishDate | 2009-06-01 |
publisher | Dove Medical Press |
record_format | Article |
series | Diabetes, Metabolic Syndrome and Obesity |
spelling | doaj.art-d66217c22bda46f580f546002150d7482023-02-02T19:36:53ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072009-06-012009default91100p38 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, PromogranTMhttp://www.dovepress.com/p38-mapk-inhibition-reduces-diabetes-induced-impairment-of-wound-heali-a3283 |
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 |
title | 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_short | p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
title_sort | p38 mapk inhibition reduces diabetes induced impairment of wound healing |
url | http://www.dovepress.com/p38-mapk-inhibition-reduces-diabetes-induced-impairment-of-wound-heali-a3283 |
work_keys_str_mv | AT satyanarayanamedicherla p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT scottwadsworth p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT bredacullen p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT dereksilcock p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT etal p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing |