The human homologue of a bovine non-selenium glutathione peroxidase is a novel keratinocyte growth factor-regulated gene.
Keratinocyte growth factor is a potent and specific mitogen for different types of epithelial cells, including keratinocytes of the skin. Furthermore, it has been implicated in morphogenetic processes of several organs. To further define the mechanisms of KGF action in the skin, we attempted to identify genes which are regulated by KGF in keratinocytes. Using the differential display RT-PCR technology, a gene was identified which was strongly induced in these cells by treatment with KGF but not with serum growth factors or pro-inflammatory cytokines. Molecular cloning of the full-length cDNA revealed a strong homology of the corresponding gene product with a bovine non-selenium glutathione peroxidase. 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, indicating a possible in vivo function of the protein in this tissue. Identification of a peroxidase as a KGF-regulated gene suggests that prevention from oxygen toxicity is a novel and specific mechanism of KGF action.
Frank
S
S
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Munz
B
B
Werner
S
S
D000595:Amino Acid Sequence; D016207:Cytokines / Q000502:physiology*; D003593:Cytoplasm / Q000201:enzymology; D018076:DNA, Complementary / Q000235:genetics; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D018507:Gene Expression Regulation, Developmental; D005979:Glutathione Peroxidase / Q000235:genetics*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011565:Psoriasis / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000201:enzymology
D016207:Cytokines; D018076:DNA, Complementary; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005979:Glutathione Peroxidase