DIFFERENTIAL EXPRESSION OF THE KERATINOCYTE GROWTH-FACTOR (KGF) AND KGF RECEPTOR GENES IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS AND ARTERIES

Keratinocyte growth factor (KGF) is a secreted member of the fibroblas t growth factor (FGF) family of heparin-binding proteins. Studies repo rted to date indicate that it functions primarily as an important para crine mediator of epithelial cell growth and differentiation. KGF appe ars to act via binding to a specific FGF receptor-2 isoform generated by an alternative splicing mechanism. To determine whether KGF may pla y a role in vascular smooth muscle cell (SMC) biology, we investigated KGF and KGF receptor gene expression in human SMC cultured in vitro a s well as in several human nonatherosclerotic artery and atheroma spec imens. KGF mRNA but not KGF receptor mRNA was expressed by SMCs, as de termined by Northern blot hybridization analysis or reverse transcript ion-polymerase chain reaction assays, respectively. Additional experim ents demonstrated that 1) human SMCs produce and secrete mitogenically active KGF and that 2) the cytokine interleukin-1 increases KGF mRNA and protein levels in human SMCs. We also found that KGF transcripts b ut not KGF receptor transcripts were expressed in control and atherosc lerotic human arteries. Taken together, these results indicate that KG F is unlikely to be involved in SMC growth regulation unless ii can fu nction intracellularly or interact with a presently unidentified KGF r eceptor. (C) 1997 Wiley-Liss, Inc.(dagger).