Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing

Jackson, CJ; Xue, M; Thompson, P; Davey, RA; Whitmont, K; Smith, S; Buisson-Legendre, N; Sztynda, T; Furphy, LJ; Cooper, A; Sambrook, P; March, L

Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing

Jackson, CJ Xue, M Thompson, P Davey, RA Whitmont, K Smith, S Buisson-Legendre, N Sztynda, T

Furphy, LJ Cooper, A Sambrook, P March, L

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Publication Type:: Journal Article
Citation:: Wound Repair and Regeneration, 2005, 13 (3), pp. 284 - 294
Issue Date:: 2005-05-01

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Field	Value	Language
dc.contributor.author	Jackson, CJ	en_US
dc.contributor.author	Xue, M	en_US
dc.contributor.author	Thompson, P	en_US
dc.contributor.author	Davey, RA	en_US
dc.contributor.author	Whitmont, K	en_US
dc.contributor.author	Smith, S	en_US
dc.contributor.author	Buisson-Legendre, N	en_US
dc.contributor.author	Sztynda, T https://orcid.org/0000-0002-8957-0864	en_US
dc.contributor.author	Furphy, LJ	en_US
dc.contributor.author	Cooper, A	en_US
dc.contributor.author	Sambrook, P	en_US
dc.contributor.author	March, L	en_US
dc.date.issued	2005-05-01	en_US
dc.identifier.citation	Wound Repair and Regeneration, 2005, 13 (3), pp. 284 - 294	en_US
dc.identifier.issn	1067-1927	en_US
dc.identifier.uri	http://hdl.handle.net/10453/4665
dc.description.abstract	Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinas, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds. Copyright © 2005 by the Wound Healing Society.	en_US
dc.relation.ispartof	Wound Repair and Regeneration	en_US
dc.relation.isbasedon	10.1111/j.1067-1927.2005.00130311.x	en_US
dc.subject.classification	Dermatology & Venereal Diseases	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Chick Embryo	en_US
dc.subject.mesh	Skin	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	Protein C	en_US
dc.subject.mesh	Wound Healing	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Neovascularization, Physiologic	en_US
dc.subject.mesh	Matrix Metalloproteinase 2	en_US
dc.title	Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	13	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	13	en_US

Abstract:

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinas, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds. Copyright © 2005 by the Wound Healing Society.

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http://hdl.handle.net/10453/4665