A STUDY ON REGULATORY MECHANISM OF GROWTH AND DIFFERENTIATION IN HUMAN KERATINOCYTES BY GROWTH FACTORS.

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(1) EGF family growth factorsWe investigated a role of HB-EGF,a new member of EGF family growth factor, in the regulatory mechanism of human keratinocyte growth. HB-EGF stimulated keratinocyte growth and keratinocytes produced HB-EGF.This showed that HB-EGF is an autocrine growth factor for human keratinocytes like TGF-alpha and amphiregulin. Furthermore, addition of HB-EGF induced production of TGF-alpha and addition of TGF-alpha increased production of HB-EGF.Taken together, auto-and cross-induction mechanism of EGF family growth factor such as HB-EGF,TGF-alpha and amphiregulin works in human keratinocytes. Localization of HB-EGF in normal and psoriatic epidermis was studied immunohistochemically. HB-EGF was present through whole epidermis including basal cells in normal skin. In psoriatic epidermis, the staining intensity of HB-EGF was markedly increased compared to normal epidermis although the localization was similar in both epidermis.(2) TGF-beta family growth factorsWe investigated the localization of TGF-beta isoforms (1,2 and 3) immunohistochemically, using antibodies specific to the precursor forms of each isoform. TGF-beta 2 was present mainly in the intercellular space of whole epidermis in normal skin. In contrast, the staining intensity of TGF-beta 2 was absent or decreased markedly in psoriatic epidermis.