Keratinocyte growth factor stimulates migration and hyaluronan synthesis in the epidermis by activation of keratinocyte hyaluronan synthases 2 and 3.
Keratinocyte growth factor (KGF) activates keratinocyte migration and stimulates wound healing. Hyaluronan, an extracellular matrix glycosaminoglycan that accumulates in wounded epidermis, is known to promote cell migration, suggesting that increased synthesis of hyaluronan might be associated with the KGF response in keratinocytes. Treatment of monolayer cultures of rat epidermal keratinocytes led to an elongated and lifted cell shape, increased filopodial protrusions, enhanced cell migration, accumulation of intermediate size hyaluronan in the culture medium and within keratinocytes, and a rapid increase of hyaluronan synthase 2 (Has2) mRNA, suggesting a direct influence on this gene. In stratified, organotypic cultures of the same cell line, both Has2 and Has3 with the hyaluronan receptor CD44 were up-regulated and hyaluronan accumulated in the epidermis, the spinous cell layer in particular. At the same time the expression of the early differentiation marker keratin 10 was inhibited, whereas filaggrin expression and epidermal permeability were less affected. The data indicate that Has2 and Has3 belong to the targets of KGF in keratinocytes, and support the idea that enhanced hyaluronan synthesis acts an effector for the migratory response of keratinocytes in wound healing, whereas it may delay keratinocyte terminal differentiation.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D004789:Enzyme Activation; D004817:Epidermis / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D016695:Glycosyltransferases; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000201:enzymology*; D008565:Membrane Proteins; D051381:Rats; D014166:Transferases; D029867:Xenopus Proteins
D017931:DNA Primers; C496455:Fgf7 protein, rat; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D029867:Xenopus Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; C491096:Has2 protein, Xenopus; C491097:Has2 protein, rat; D000076002:Hyaluronan Synthases