Cargando…

HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells

The regulated recruitment and differentiation of multipotent bone marrow-derived cells (BMDCs) to sites of injury are critical for efficient wound healing. Previously we demonstrated that sustained expression of HOXA3 both accelerated wound healing and promoted angiogenesis in diabetic mice. In this...

Descripción completa

Detalles Bibliográficos
Autores principales: Mace, Kimberly A, Restivo, Terry E, Rinn, John L, Paquet, Agnes C, Chang, Howard Y, Young, David M, Boudreau, Nancy J
Formato: Texto
Lenguaje:English
Publicado: Wiley Subscription Services, Inc., A Wiley Company 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733377/
https://www.ncbi.nlm.nih.gov/pubmed/19544454
http://dx.doi.org/10.1002/stem.90
_version_ 1782171103155716096
author Mace, Kimberly A
Restivo, Terry E
Rinn, John L
Paquet, Agnes C
Chang, Howard Y
Young, David M
Boudreau, Nancy J
author_facet Mace, Kimberly A
Restivo, Terry E
Rinn, John L
Paquet, Agnes C
Chang, Howard Y
Young, David M
Boudreau, Nancy J
author_sort Mace, Kimberly A
collection PubMed
description The regulated recruitment and differentiation of multipotent bone marrow-derived cells (BMDCs) to sites of injury are critical for efficient wound healing. Previously we demonstrated that sustained expression of HOXA3 both accelerated wound healing and promoted angiogenesis in diabetic mice. In this study, we have used green fluorescent protein-positive bone marrow chimeras to investigate the effect of HOXA3 expression on recruitment of BMDCs to wounds. We hypothesized that the enhanced neovascularization induced by HOXA3 is due to enhanced mobilization, recruitment, and/or differentiation of BMDCs. Here we show that diabetic mice treated with HOXA3 displayed a significant increase in both mobilization and recruitment of endothelial progenitor cells compared with control mice. Importantly, we also found that HOXA3-treated mice had significantly fewer inflammatory cells recruited to the wound compared with control mice. Microarray analyses of HOXA3-treated wounds revealed that indeed HOXA3 locally increased expression of genes that selectively promote stem/progenitor cell mobilization and recruitment while also suppressing expression of numerous members of the proinflammatory nuclear factor κB pathway, including myeloid differentiation primary response gene 88 and toll-interacting protein. Thus HOXA3 accelerates wound repair by mobilizing endothelial progenitor cells and attenuating the excessive inflammatory response of chronic wounds.
format Text
id pubmed-2733377
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Wiley Subscription Services, Inc., A Wiley Company
record_format MEDLINE/PubMed
spelling pubmed-27333772009-09-02 HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells Mace, Kimberly A Restivo, Terry E Rinn, John L Paquet, Agnes C Chang, Howard Y Young, David M Boudreau, Nancy J Stem Cells Tissue-Specific Stem Cells The regulated recruitment and differentiation of multipotent bone marrow-derived cells (BMDCs) to sites of injury are critical for efficient wound healing. Previously we demonstrated that sustained expression of HOXA3 both accelerated wound healing and promoted angiogenesis in diabetic mice. In this study, we have used green fluorescent protein-positive bone marrow chimeras to investigate the effect of HOXA3 expression on recruitment of BMDCs to wounds. We hypothesized that the enhanced neovascularization induced by HOXA3 is due to enhanced mobilization, recruitment, and/or differentiation of BMDCs. Here we show that diabetic mice treated with HOXA3 displayed a significant increase in both mobilization and recruitment of endothelial progenitor cells compared with control mice. Importantly, we also found that HOXA3-treated mice had significantly fewer inflammatory cells recruited to the wound compared with control mice. Microarray analyses of HOXA3-treated wounds revealed that indeed HOXA3 locally increased expression of genes that selectively promote stem/progenitor cell mobilization and recruitment while also suppressing expression of numerous members of the proinflammatory nuclear factor κB pathway, including myeloid differentiation primary response gene 88 and toll-interacting protein. Thus HOXA3 accelerates wound repair by mobilizing endothelial progenitor cells and attenuating the excessive inflammatory response of chronic wounds. Wiley Subscription Services, Inc., A Wiley Company 2009-07 /pmc/articles/PMC2733377/ /pubmed/19544454 http://dx.doi.org/10.1002/stem.90 Text en Copyright © 2009 AlphaMed Press http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Tissue-Specific Stem Cells
Mace, Kimberly A
Restivo, Terry E
Rinn, John L
Paquet, Agnes C
Chang, Howard Y
Young, David M
Boudreau, Nancy J
HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells
title HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells
title_full HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells
title_fullStr HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells
title_full_unstemmed HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells
title_short HOXA3 Modulates Injury-Induced Mobilization and Recruitment of Bone Marrow-Derived Cells
title_sort hoxa3 modulates injury-induced mobilization and recruitment of bone marrow-derived cells
topic Tissue-Specific Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733377/
https://www.ncbi.nlm.nih.gov/pubmed/19544454
http://dx.doi.org/10.1002/stem.90
work_keys_str_mv AT macekimberlya hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells
AT restivoterrye hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells
AT rinnjohnl hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells
AT paquetagnesc hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells
AT changhowardy hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells
AT youngdavidm hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells
AT boudreaunancyj hoxa3modulatesinjuryinducedmobilizationandrecruitmentofbonemarrowderivedcells