Frank S, Munz B, Werner S
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Oncogene. 1997 Feb 27;14(8):915-21. doi: 10.1038/sj.onc.1200905.
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.
角质形成细胞生长因子是一种针对不同类型上皮细胞（包括皮肤角质形成细胞）的强效特异性促有丝分裂原。此外，它还与多个器官的形态发生过程有关。为了进一步明确角质形成细胞生长因子在皮肤中的作用机制，我们试图鉴定在角质形成细胞中受角质形成细胞生长因子调控的基因。利用差异显示逆转录聚合酶链反应技术，鉴定出一个基因，该基因在用角质形成细胞生长因子处理的这些细胞中被强烈诱导，但在用血清生长因子或促炎细胞因子处理时未被诱导。全长互补DNA的分子克隆显示相应基因产物与牛非硒谷胱甘肽过氧化物酶有很强的同源性。用全长互补DNA转染COS细胞后，获得了一种预期大小为27kD的细胞质蛋白，其具有谷胱甘肽过氧化物酶的大小。在正常人类皮肤中检测到该新基因的表达，在银屑病皮肤中表达水平特别高，表明该蛋白在该组织中可能具有体内功能。鉴定出一种过氧化物酶作为角质形成细胞生长因子调控的基因表明，预防氧毒性是角质形成细胞生长因子作用的一种新的特异性机制。
