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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-16
pubmed:abstractText
Keratinocyte migration is essential for the rapid closure of the epidermis in the process of wound healing. Mesenchymal cell-derived hepatocyte growth factor (HGF) is a central regulator of this process. However, the molecular mechanisms and relevant genes that facilitate this cellular response are still poorly defined. We used heterologous cocultures combining primary human keratinocytes and genetically modified murine fibroblasts to identify key factors mediating HGF-induced epidermal cell migration. The absence of c-Jun activity in fibroblasts completely abolished the expression of HGF in these cells and consequently altered the behavior of keratinocytes. Time-resolved expression series of keratinocytes stimulated with HGF disclosed target genes regulating HGF-dependent motility. In addition to well-established HGF-dependent wound healing-associated genes, carcinoembryogenic antigen-related cell adhesion molecule (CEACAM)-1 and the urokinase plasminogen activator (uPA)/uPA-receptor (uPAR) pathway were identified as possible mediators in HGF-induced keratinocyte migration. The functional relevance of CEACAM-1 and uPA/uPAR on epidermal cell motility was demonstrated using the HaCaT cell culture model. In conclusion, the distinct spatiotemporal regulation of genes by HGF is essential for proper epidermal cell migration in cutaneous wound healing.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1523-1747
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1140-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
AP-1-controlled hepatocyte growth factor activation promotes keratinocyte migration via CEACAM1 and urokinase plasminogen activator/urokinase plasminogen receptor.
pubmed:affiliation
Institute of Pathology, University Hospital of Heidelberg, Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't