Analysis of regulatory mechanism of various growth factors in the growth and differentiation of human keratinocytes and fibroblasts

点击翻译按钮获取中文摘要

The summary of our research results was classified into three groups : 1) EGF family growth factors, 2) TGF-beta, 3) Epidermal cell diferrentiation inhibitor(EDIN). Concerning to EGF family growth factors, it was known that TGF-alpha and amphiregulin were autocrine growth factors for human keratinocytes. They stimulate the growth of human ketatinocytes and produced by human keratinocytes. In this study, we showed that heparin-binding EGF-like growth factor(HB-EGF), a new member of EGF family growth factor, is also an autocrine growth factor for human keratinocytes. The localization of HB-EGF in normal and psoriatic epidermis was also shown by immunohistochemical methods. Interestingly, an mutual stimulatory mechanism of these EGF family growth factors was revealed : the addtion of HB-EGF or TGF-alpha increased all of HB-EGF mRNA, TGF-alpha mRNA and amphiregulin mRNA.So, this is a very effecttive mechanism for induction of autocrine EGF family growth factors. It will be one of the main aims in the future study on growth regulation of human keratinocytes. Concerning to TGF-beta, we identified the localization of TGF-beta isoforms in the human skin. In the normal human skin, TGF-beta2 is localized in the epidermis and TGF-beta3 is localized mainly in the upper dermis. Interestingly, the staining intensity of TGF-beta2 was decreased in the epidermis of psoriatic lesions. This may be correlated with the epidermal hyperplasia in psorisis. Concerning to EDIN, it was purified from the supernatant of Staphylococcus aureus. It inhibits the differentiation of human ketatinocytes. We demonstrated that EDIN ADP-ribosylates rho protein, one of small G proteins and inserts its effect.