Molecular Mechanism of Epithelial-Mesenchymal Interactions

1.胃上皮细胞分化机制：胎鼠胃上皮细胞在无间充质的情况下，在原代培养中分化为表达组织蛋白酶E的表面粘液细胞，但与间充质共培养时，培养的上皮细胞中出现了许多(20-80%，视培养条件而定)表达胃蛋白酶原的细胞。然而，即使在同基因宿主的肾被膜下培养，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会自动分化，(2)间充质是粘液颈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(如神经刺激)。肝细胞生长因子(HGF)在腺胃中的作用：我们先前报道了HGF区域特异性刺激原代培养的胃肠上皮生长，并满足了HGF介导的腺胃上皮-间充质相互作用。在这里，我们检测了HGF及其受体在发育中的腺胃中的表达。定量RT-PCR结果显示，HGF及其受体在妊娠17-18天由复层上皮转化为单纯腺上皮时表达最强，提示HGF控制着上皮的形态发生。HGF激活剂(HGFA)激活HGF：最近报道HGF由间充质以非活性前体形式分泌，并在HGFA的作用下被激活。对HGFA在发育中的胃肠道的表达检测发现，HGFA仅在上皮细胞中表达，在间质中不表达，HGFA在结肠中高表达，在小肠和腺胃中中等表达，在前胃中很少表达。

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.