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Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6.

Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts.

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1
Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), Singapore.

Abstract

Wound healing is a complex process involving a number of related genes and receptors. Using cDNA microarrays, we explored the global gene expression profile of phenytoin (20microg/ml) induced changes to human dermal fibroblasts. Microarray data analysis revealed approximately 1500 genes were differentially expressed by 2.5-fold. At 3, 6, 12, and 24h, the transcripts of the major growth factors involved in wound healing and their receptors were increased. This was further confirmed by RT-PCR. Genes encoding other proteins with roles in signal transduction (NFkappaB), extracellular matrix (MMP1) including type I collagen, fibronectin, and laminin were strongly induced at 6h and onwards. Genes involved in cell cycle regulation (CCND1 and CDKN1A) were down-regulated consistent with our finding that phenytoin per se did not have cell proliferation activity. Notably, phenytoin accelerates the autocrine and paracrine activity of growth factors by up-regulating the related receptors.

PMID:
14741686
DOI:
10.1016/j.bbrc.2003.12.146
[Indexed for MEDLINE]

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