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Molecular Mechanism of Epithelial-Mesenchymal Interactions

上皮-间质相互作用的分子机制

基本信息

批准号：
08680787
负责人：
FUKAMACHI Hiroshi
金额：
$ 1.47万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

1. Mechanism of Gastric Epithelial Differentiation : In the avsence of mesenchymes, fetal rat gastric epithelial cells differentiated into surface mucous cells which express cathepsin E in primary culture, but when cocultured with mesenchymes, many (20-80%, depending on culture condition) pepsinogen-expressing cells appeared in the epithelial cells in culture. Parietal cells, however, never differentiated even when the cells were cultured under the kidney capsule of syngeneic hosts. Thus, we conclude that (1) surface mucous cells antonomously dfferentiate in the absence of any inducing factors, (2) mesenchymes are necessary for the differentiation of mucous neck and chief cells, and (3) other inducing factors (such as nervous stimuli) would be needed for the differentiation of parietal cells.2. The role of Hepatocyte Growth Factor (HGF) in the Glandular Stomach : We have previously reported that HGF region-specifically stimulates gastro-intestinal epithelial growth in primary culture, and suffested that HGF mediates epithelial-mesenchymal interaction in the glandular stomach. Here we examined the expression of HGF and its receptor in the developing glandular stomach. Quantitative RT-PCR showed that expression of both HGF and its receptor was highest at 17-18 days of gestation when the epithelia are converted form stratified to simple glandular ones, indicating that HGF control the epithelial morphogenesis.3. Activation of HGF by HGF activator (HGFA) : It is recently reported that HGF is secreted from mesenchyme as inactive pro-form, and activated by the action of HGFA.Examination of HGFA expression in developing gastro-intestinal tract revealed that HGFA is expressed only in epithelia but not in mesenchymes, and that HGFA is expressed highly in the colon, moderately in the small intestine and glandular stomach, little in forestomach.

1.胃上皮细胞分化的机制：在无间充质的情况下，胎鼠胃上皮细胞在原代培养中分化为表达组织蛋白酶E的表面粘液细胞，但当与间充质共培养时，培养的上皮细胞中出现许多（20- 80%，取决于培养条件）表达胃蛋白酶原的细胞。然而，即使将壁细胞培养在同系宿主的肾囊下，壁细胞也从未分化。因此，我们得出结论：（1）表面粘液细胞在没有任何诱导因素的情况下发生异常分化，（2）间充质是粘液颈细胞和主细胞分化所必需的，（3）壁细胞的分化需要其他诱导因素（例如神经刺激）。2.肝细胞生长因子（HGF）在腺胃中的作用：我们以前曾报道过HGF区域特异性刺激原代培养的胃肠上皮生长，并证实HGF介导腺胃中上皮-间质相互作用。在这里，我们研究了肝细胞生长因子及其受体在腺胃发育的表达。定量RT-PCR结果显示，HGF及其受体在妊娠17-18 d时表达最高，此时上皮由复层上皮向单层腺上皮转化，说明HGF控制着上皮的形态发生. HGF激活剂（HGFA）对HGF的激活作用：近年来研究发现，HGF是间充质细胞分泌的无活性前体，在HGFA的作用下被激活，HGFA在胃肠道发育过程中的表达显示，HGFA仅在上皮细胞中表达，在间充质细胞中不表达，在结肠中表达量高，在小肠和腺胃中表达量中等，在前胃中表达量低。