SUPPRESSION OF KERATINOCYTE GROWTH-FACTOR EXPRESSION BY GLUCOCORTICOIDS IN-VITRO AND DURING WOUND-HEALING

We have recently demonstrated an important function of keratinocyte gr owth factor (KGF) in morphogenesis of epithelium and wound re-epitheli alization. Furthermore, abnormalities in KGF expression or responsiven ess are associated with wound-healing defects. In this study we have a nalyzed the regulation of KGF expression during wound repair in glucoc orticoid-treated mice that are characterized by severe wound healing a bnormalities. Induction of KGF mRNA expression after skin injury was s ignificantly reduced in these mice, whereas KGF receptor mRNA levels w ere only affected to a minor extent by glucocorticoid treatment. The r educed KGF expression during wound healing in steroid-treated animals is at least partially due to a direct effect of glucocorticoids on the KGF expressing mesenchymal cells, because treatment of cultured fibro blasts with dexamethasone reduced KGF mRNA levels in a time- and conce ntration-dependent manner. The inhibitory effect of glucocorticoids on KGF expression was compensated for by high levels of serum growth fac tors or pro-inflammatory cytokines, demonstrating that KGF expression is subject to positive and negative regulation. Thus it seems likely t hat a fine balance of various KGF-regulating factors is important for normal wound healing.