A NOVEL TYPE OF GLUTATHIONE-PEROXIDASE - EXPRESSION AND REGULATION DURING WOUND REPAIR

We have previously identified and cloned a novel keratinocyte growth f actor (KGF)-regulated gene in human keratinocytes that encodes the hum an homologue of a bovine non-selenium glutathione peroxidase (GPx). To gain insight into the regulation of this gene in vivo, we isolated th e murine homologue from a mouse skin cDNA library. in vitro transcript ion/translation demonstrated that the cDNA encodes a 27 kDa protein. F urthermore, we amplified by PCR a partial cDNA that most likely corres ponds to a related gene. RNase protection analysis revealed tissue-spe cific expression of both genes and the occurrence of alternative splic ing or RNA editing of at least one of the primary transcripts. Similar to that of KGF, expression of GPx was strongly induced after cutaneou s injury, and each isoform displayed unique kinetics of expression dur ing the repair process. In situ hybridization studies demonstrated hig h levels of GPx mRNA in keratinocytes of the hyperproliferative epithe lium at the wound edge. Since these cells express functional KGF recep tors, induction of GPx expression by KGF might also occur in vivo. The se data suggest a role for GPx in the protection of epithelial cells a gainst oxidative stress, particularly during the inflammatory phase of wound repair.