Keratinocyte growth factor expression in human gingival fibroblasts and stimulation of in vitro gene expression by retinoic acid

Background: Keratinocyte growth factor (KGF) is a stromally derived growth factor of the fibroblast growth factor (FGF) family with paracrine effects targeted to influence the growth and differentiation of epithelia. Regional and temporal changes in KGF expression play important roles in the develop ment and maintenance of epithelial structures and in epithelial wound heali ng. Differing patterns of expression of KGF by fibroblasts in the gingival region could therefore be related to the observed regional variation in the differentiation and behavior of gingival epithelia. Methods: The in vitro and in vivo patterns of expression of KGF mRNA in hum an gingival and periodontal fibroblasts were examined using reverse transcr iption polymerase chain reactions (RT-PCR) and in situ hybridization with d igoxigenin-labeled riboprobes. The patterns observed for human gingiva were compared with those for human skin and for murine tissues. Results: Gingival and periodontal fibroblasts showed expression of KGF tran scripts in vitro, and the degree of expression was markedly influenced by t he presence of retinoic acid, an agent known to influence patterns of epith elial differentiation. Sections of human and murine gingiva and skin showed regionally variable expression of transcripts with the cells expressing KG F in the subepithelial, rather than the deeper, connective tissues and peri odontium. Conclusions: The results point to a role of KGF in the maintenance of norma l growth and differentiation of gingival epithelia. A lack of KGF expressio n by periodontal fibroblasts in vivo is expected to hinder apical epithelia l migration and thus stabilize the epithelial attachment. The effects of re tinoic acid (RA) on KGF expression in vitro provide an indirect mechanism b y which RA may regulate the growth and differentiation of gingival epitheli a.