p38 MAPK inhibition reduces diabetes-induced impairment of wound healing

Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing&nbsp;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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Satyanarayana Medicherla, Scott Wadsworth, Breda Cullen, Derek Silcock, et al.
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/d66217c22bda46f580f546002150d748
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d66217c22bda46f580f546002150d748
record_format	dspace
spelling	oai:doaj.org-article:d66217c22bda46f580f546002150d7482021-12-02T06:39:37Zp38 MAPK inhibition reduces diabetes-induced impairment of wound healing1178-7007https://doaj.org/article/d66217c22bda46f580f546002150d7482009-06-01T00:00:00Zhttp://www.dovepress.com/p38-mapk-inhibition-reduces-diabetes-induced-impairment-of-wound-heali-a3283https://doaj.org/toc/1178-7007Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing&nbsp;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 &amp; 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 p38&alpha;-selective inhibitor, SCIO-469, was applied topically and&nbsp;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 &micro;g/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&nbsp;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 Satyanarayana MedicherlaScott WadsworthBreda CullenDerek Silcocket al.Dove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2009, Iss default, Pp 91-100 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Satyanarayana Medicherla Scott Wadsworth Breda Cullen Derek Silcock et al. p38 MAPK inhibition reduces diabetes-induced impairment of wound healing
description	Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing&nbsp;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 &amp; 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 p38&alpha;-selective inhibitor, SCIO-469, was applied topically and&nbsp;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 &micro;g/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&nbsp;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
format	article
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
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
publishDate	2009
url	https://doaj.org/article/d66217c22bda46f580f546002150d748
work_keys_str_mv	AT satyanarayanamedicherla p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT scottwadsworth p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT bredacullen p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT dereksilcock p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing AT etal p38mapkinhibitionreducesdiabetesinducedimpairmentofwoundhealing
_version_	1718399840300302336

p38 MAPK inhibition reduces diabetes-induced impairment of wound healing

Ejemplares similares