权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

多种生长因子对人角质形成细胞和成纤维细胞生长分化的调控机制分析

基本信息

批准号：
03454273
负责人：
YOSHIKAWA Kunihiko
金额：
$ 4.29万
依托单位：
Osasa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

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.

我们的研究结果归纳为三大类：1）EGF家族生长因子，2）TGF-β，3）表皮细胞分化抑制剂（EDIN）。关于EGF家族生长因子，已知TGF-α和双调蛋白是人角质形成细胞的自分泌生长因子。它们刺激人ketatinocytes的生长并由人角质形成细胞产生。在本研究中，我们发现肝素结合EGF样生长因子（HB-EGF），EGF家族生长因子的新成员，也是一种自分泌的人角质形成细胞生长因子。免疫组织化学方法显示HB-EGF在正常表皮和银屑病表皮中的定位。有趣的是，这些EGF家族生长因子之间存在相互促进的机制：加入HB-EGF或TGF-α后，HB-EGF mRNA、TGF-α mRNA和双调蛋白mRNA均增加，这是诱导EGF家族生长因子自分泌的一种非常有效的机制。这将是今后研究人角质形成细胞生长调控的主要方向之一。关于TGF-β，我们鉴定了TGF-β同种型在人皮肤中的定位。在正常人皮肤中，TGF-β 2位于表皮中，TGF-β 3主要位于真皮上层。有趣的是，在银屑病皮损的表皮中TGF-β 2的染色强度降低。这可能与银屑病的表皮增生有关。EDIN是从金黄色葡萄球菌培养上清中纯化得到的。它抑制人ketatinocytes的分化。我们证明了EDIN ADP-核糖基化rho蛋白，一种小G蛋白，并插入其作用。