Cargando…

A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling

Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPI...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Liqiang, Yaron, Jordan R., Tafoya, Amanda M., Wallace, Sarah E., Kilbourne, Jacquelyn, Haydel, Shelley, Rege, Kaushal, McFadden, Grant, Lucas, Alexandra R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832452/
https://www.ncbi.nlm.nih.gov/pubmed/31590323
http://dx.doi.org/10.3390/jcm8101626
_version_ 1783466175706955776
author Zhang, Liqiang
Yaron, Jordan R.
Tafoya, Amanda M.
Wallace, Sarah E.
Kilbourne, Jacquelyn
Haydel, Shelley
Rege, Kaushal
McFadden, Grant
Lucas, Alexandra R.
author_facet Zhang, Liqiang
Yaron, Jordan R.
Tafoya, Amanda M.
Wallace, Sarah E.
Kilbourne, Jacquelyn
Haydel, Shelley
Rege, Kaushal
McFadden, Grant
Lucas, Alexandra R.
author_sort Zhang, Liqiang
collection PubMed
description Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases and inflammation, in a mouse excisional wound model. Saline or recombinant Serp-1 were applied directly to wounds as single doses of 1 μg or 2 µg or as two 1 µg boluses. A chitosan-collagen hydrogel was also tested for Serp-1 delivery. Wound size was measured daily for 15 days and scarring assessed by Masson’s trichrome, Herovici’s staining, and immune cell dynamics and angiogenesis by immunohistochemistry. Serp-1 treatment significantly accelerated wound healing, but was blocked by urokinase-type plasminogen activator (uPAR) antibody. Repeated dosing at a lower concentration was more effective than single high-dose serpin. A single application of Serp-1-loaded chitosan-collagen hydrogel was as effective as repeated aqueous Serp-1 dosing. Serp-1 treatment of wounds increased arginase-1-expressing M2-polarized macrophage counts and periwound angiogenesis in the wound bed. Collagen staining also demonstrated that Serp-1 improves collagen maturation and organization at the wound site. Serp-1 has potential as a safe and effective immune modulating treatment that targets thrombolytic proteases, accelerating healing and reducing scar in deep cutaneous wounds.
format Online
Article
Text
id pubmed-6832452
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68324522019-11-25 A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling Zhang, Liqiang Yaron, Jordan R. Tafoya, Amanda M. Wallace, Sarah E. Kilbourne, Jacquelyn Haydel, Shelley Rege, Kaushal McFadden, Grant Lucas, Alexandra R. J Clin Med Article Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases and inflammation, in a mouse excisional wound model. Saline or recombinant Serp-1 were applied directly to wounds as single doses of 1 μg or 2 µg or as two 1 µg boluses. A chitosan-collagen hydrogel was also tested for Serp-1 delivery. Wound size was measured daily for 15 days and scarring assessed by Masson’s trichrome, Herovici’s staining, and immune cell dynamics and angiogenesis by immunohistochemistry. Serp-1 treatment significantly accelerated wound healing, but was blocked by urokinase-type plasminogen activator (uPAR) antibody. Repeated dosing at a lower concentration was more effective than single high-dose serpin. A single application of Serp-1-loaded chitosan-collagen hydrogel was as effective as repeated aqueous Serp-1 dosing. Serp-1 treatment of wounds increased arginase-1-expressing M2-polarized macrophage counts and periwound angiogenesis in the wound bed. Collagen staining also demonstrated that Serp-1 improves collagen maturation and organization at the wound site. Serp-1 has potential as a safe and effective immune modulating treatment that targets thrombolytic proteases, accelerating healing and reducing scar in deep cutaneous wounds. MDPI 2019-10-04 /pmc/articles/PMC6832452/ /pubmed/31590323 http://dx.doi.org/10.3390/jcm8101626 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Liqiang
Yaron, Jordan R.
Tafoya, Amanda M.
Wallace, Sarah E.
Kilbourne, Jacquelyn
Haydel, Shelley
Rege, Kaushal
McFadden, Grant
Lucas, Alexandra R.
A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling
title A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling
title_full A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling
title_fullStr A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling
title_full_unstemmed A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling
title_short A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling
title_sort virus-derived immune modulating serpin accelerates wound closure with improved collagen remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832452/
https://www.ncbi.nlm.nih.gov/pubmed/31590323
http://dx.doi.org/10.3390/jcm8101626
work_keys_str_mv AT zhangliqiang avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT yaronjordanr avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT tafoyaamandam avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT wallacesarahe avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT kilbournejacquelyn avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT haydelshelley avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT regekaushal avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT mcfaddengrant avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT lucasalexandrar avirusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT zhangliqiang virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT yaronjordanr virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT tafoyaamandam virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT wallacesarahe virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT kilbournejacquelyn virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT haydelshelley virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT regekaushal virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT mcfaddengrant virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling
AT lucasalexandrar virusderivedimmunemodulatingserpinaccelerateswoundclosurewithimprovedcollagenremodeling