Document Detail


HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair.
MedLine Citation:
PMID:  15914537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Wound repair requires both the recruitment and coordination of numerous cell types including inflammatory cells, fibroblasts, endothelial and epithelial cells. Each cell type has a distinct set of cell behavior such as formation of granulation tissue and basement membrane, migration, proliferation and redifferentiation. These processes are dependent on cell-cell and cell-ECM signaling, intracellular signal transduction cascades, and ultimately, changes in gene transcription. We have investigated the role of the transcription factor HOXA3 in wound repair and angiogenesis. Here we show that HOXA3 increases endothelial cell migration, induces angiogenesis in vivo, and leads to increased expression of the matrix metalloproteinase-14 (MMP-14) and urokinase-type plasminogen activator receptor (uPAR) genes in endothelial cells in culture and in vivo in response to injury. We find that HOXA3 gene expression is upregulated during wound healing in angiogenic endothelial cells and keratinocytes, and that HOXA3 is not induced in genetically diabetic mice that have impaired angiogenesis and wound repair. We demonstrate that gene transfer of HOXA3 into diabetic mouse wounds leads to dramatic improvements in both angiogenesis and wound closure. In addition, we show that HOXA3 promotes migration of endothelial cells and keratinocytes in a uPAR-dependent manner. Together these findings illustrate how the morphoregulatory protein, HOXA3 can facilitate tissue remodeling via coordinated changes in both epithelial and endothelial cell gene expression and behavior in adult tissues during wound repair.
Authors:
Kimberly A Mace; Scott L Hansen; Connie Myers; David M Young; Nancy Boudreau
Related Documents :
18212537 - The role of beta-1,4-galactosyltransferase-i in the skin wound-healing process.
16689737 - Fibrin structure and wound healing.
15705727 - Vascular endothelial wound closure under shear stress: role of membrane fluidity and fl...
14751957 - Use of tissue adhesives in sport? a new application in international ice hockey.
24280217 - Il-4 induces up-regulation of endothelial cell claudin-5 through activation of foxo1: r...
21108827 - Airway branching morphogenesis in three dimensional culture.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-05-24
Journal Detail:
Title:  Journal of cell science     Volume:  118     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-09     Completed Date:  2005-10-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2567-77     Citation Subset:  IM    
Affiliation:
Surgical Research Laboratory, Department of Surgery, University of California San Francisco, San Francisco General Hospital, CA 94110, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Angiogenic Proteins / genetics,  metabolism
Animals
Cell Movement* / drug effects
Cells, Cultured
Endothelial Cells / cytology,  metabolism*
Epithelial Cells / cytology,  metabolism*
Homeodomain Proteins / genetics,  metabolism*
Humans
Keratinocytes / cytology,  metabolism
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases / metabolism
Mice
Mice, Inbred NOD
Neovascularization, Physiologic*
Receptors, Cell Surface / metabolism
Receptors, Urokinase Plasminogen Activator
Skin / cytology
Transcriptional Activation / genetics
Up-Regulation / genetics
Wound Healing / physiology*
Grant Support
ID/Acronym/Agency:
CA85249/CA/NCI NIH HHS; F32GM2084901/GM/NIGMS NIH HHS; K08GM00674/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Angiogenic Proteins; 0/Homeodomain Proteins; 0/Hoxa3 protein, mouse; 0/PLAUR protein, human; 0/Plaur protein, mouse; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated; EC 3.4.24.-/Metalloendopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-de...
Next Document:  The formin family protein CaBni1p has a role in cell polarity control during both yeast and hyphal g...