Cargando…
p38 MAPK inhibition reduces diabetes-induced impairment of wound healing
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 nonreso...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048002/ https://www.ncbi.nlm.nih.gov/pubmed/21437122 |
_version_ | 1782199118807957504 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Medicherla, Satyanarayana |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3048002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30480022011-03-23 p38 MAPK inhibition reduces diabetes-induced impairment of wound healing 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 Diabetes Metab Syndr Obes Commentary 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. Dove Medical Press 2009-06-23 /pmc/articles/PMC3048002/ /pubmed/21437122 Text en © 2009 Medicherla et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Commentary 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 p38 MAPK inhibition reduces diabetes-induced impairment of wound healing |
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 |
topic | Commentary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048002/ https://www.ncbi.nlm.nih.gov/pubmed/21437122 |
work_keys_str_mv | AT medicherlasatyanarayana p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT wadsworthscott p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT cullenbreda p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT silcockderek p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT majingy p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT mangaduruban p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT kerrirene p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT chakravartysarvajit p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT luedtkegregoryl p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT dugarsundeep p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT protterandrewa p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT higginslindas p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing |