CELL-TYPE-SPECIFIC INHIBITION OF KERATINOCYTE COLLAGENASE-1 EXPRESSION BY BASIC FIBROBLAST GROWTH-FACTOR AND KERATINOCYTE GROWTH-FACTOR - ACOMMON RECEPTOR PATHWAY

Collagenase-1 is invariantly expressed by migrating basal keratinocyte s in all forms of human skin wounds, and its expression is induced by contact with native type I collagen, However, net differences in enzym e production between acute and chronic wounds may be modulated by solu ble factors present within the tissue environment, Basic fibroblast gr owth factor (bFGF, FGF-2;) and keratinocyte growth factor (KGF, FGF-9) , which are produced during wound healing, inhibited collagenase-1 exp ression by keratinocytes in a dose dependent manner, However, KGF was >100-fold more effective than bFGF at inhibiting collagenase-1 express ion, suggesting that this differential signaling is transduced via an FGF receptor that binds these ligands with different affinities, Rever se transcriptase-polymerase chain reaction analysis of human keratinoc yte mRNA for fibroblast growth factor receptors (FGFRs) revealed expre ssion of only FGFR-2 IIIb, the KGF-specific receptor, which also binds bFGF with low affinity, and FGFR-3 IIIb, which does not bind bFGF or KGF, FGFRs that bind bFGF with high affinity were not detected, Our re sults suggest that bFGF and KGF inhibit collagenase-1 expression throu gh the KGF cell-surface receptor (FG;FR-P IIIb), Because bFGF induces collagenase-1 in most cell types, cell-specific expression of FGFR fam ily members may dictate the regulation of matrix metalloproteinases in a tissue-specific manner.