STIMULATION OF ALL EPITHELIAL ELEMENTS DURING SKIN REGENERATION BY KERATINOCYTE GROWTH-FACTOR

Keratinocyte growth factor (KGF), a recently discovered 18.9 kD member of the fibroblast growth factor family has been shown to selectively induce keratinocyte proliferation and differentiation in tissue cultur e. To explore its potential stimulating keratinocyte growth and differ entiation in vivo, we analyzed for the influence of KGF on epithelial derived elements within a wound created through the cartilage on the r abbit ear. KGF accelerated reepithelialization (p = 0.004) and increas ed the thickness of the epithelium (p = 0.0005) when 4-40 mu g/cm(2) r ecombinant KGF was added at the time of wounding. The regenerating epi dermis showed normal differentiation as detected by cytokeratin immuno staining. Remarkably, however, KGF stimulated proliferation and differ entiation of early progenitor cells within hair follicles and sebaceou s glands in the wound bed and adjacent dermis. There was a transient b ut highly significant increase in specific labeling of cycling cells i n both basal and suprabasal layers that extended into the spinous laye r of the regenerating epidermis. As an indication of specificity, the inflammatory cells and fibroblasts within the wound were not influence d by KGF. The results indicate that KGF is unique in its ability to ac celerate reepithelialization and dermal regeneration by targeting mult iple epithelial elements within the skin. These results suggest that K GF may induce specific epithelial progenitor cell lineages within the skin to proliferate and differentiate, and thus may be a critical dete rminant of regeneration of skin. Furthermore, these findings illustrat e the potential capacity of this system to analyze epithelial differen tiation programs and disorders of epidermis, dermal glandular elements , and hair follicles.