THE HUMAN HOMOLOG OF A BOVINE NONSELENIUM GLUTATHIONE-PEROXIDASE IS ANOVEL KERATINOCYTE GROWTH FACTOR-REGULATED GENE

Keratinocyte growth factor is a potent and specific mitogen for differ ent types of epithelial cells, including keratinocytes of the skin. Fu rthermore, it has been implicated in morphogenetic processes of severa l organs. To further define the mechanisms of KGF action in the skin, we attempted to identify genes which are regulated by KGF in keratinoc ytes. Using the differential display RT-PCR technology, a gene was ide ntified which was strongly induced in these cells by treatment with KG F but not with serum growth factors or pro-inflammatory cytokines. Mol ecular cloning of the full-length cDNA revealed a strong homology of t he corresponding gene product with a bovine non-selenium glutathione p eroxidase. Upon transfection of COS cells with the full-length cDNA, a 27 kD cytoplasmic protein was obtained which had the expected size of glutathione peroxidase. Expression of the novel gene was detected in normal human skin and at particularly high levels in psoriatic skin, i ndicating a possible in vivo function of the protein in this tissue. I dentification of a peroxidase as a KGF-regulated gene suggests that pr evention from oxygen toxicity is a novel and specific mechanism of KGF action.