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

(1)EGF家族生长因子我们研究了EGF家族生长因子的新成员HB-EGF在人角质形成细胞生长调节机制中的作用。HB-EGF刺激角质形成细胞生长，角质形成细胞产生HB-EGF，这表明HB-EGF是人角质形成细胞的自分泌生长因子，类似于TGF-α和双调蛋白。此外，加入HB-EGF诱导TGF-α的产生和加入TGF-α增加HB-EGF的产生。总之，EGF家族生长因子如HB-EGF、TGF-α和双调蛋白的自身和交叉诱导机制在人角质形成细胞中起作用。用免疫组化方法研究了正常人和银屑病患者表皮中HB-EGF的定位。在正常皮肤中，HB-EGF存在于整个表皮，包括基底细胞。在银屑病表皮中，HB-EGF的染色强度明显高于正常表皮，尽管两者的定位相似。(2)TGF-β家族生长因子我们用化学方法研究了TGF-β同种型（1、2和3）的定位，使用对每种同种型的前体形式特异的抗体。TGF-β 2在正常皮肤中主要分布于整个表皮的细胞间隙。与此相反，TGF-β 2的染色强度在银屑病表皮中不存在或显著降低。

(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.