Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts.
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.
Swamy
S M K
SM
Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), Singapore.
Tan
P
P
Zhu
Y Z
YZ
Lu
J
J
Achuth
H N
HN
Moochhala
S
S
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D016000:Cluster Analysis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010672:Phenytoin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D012333:RNA, Messenger; D010672:Phenytoin