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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...

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Autores principales: 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
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
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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.
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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
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