Molecular Mechanism of Epithelial-Mesenchymal Interactions

1. 胃上皮细胞的分化机制：在没有间充质的情况下，胎鼠胃上皮细胞在原代培养中分化为表达组织蛋白酶E的表面粘膜细胞，但与间充质共培养时，培养的上皮细胞中出现了许多（20-80%，取决于培养条件）表达胃蛋白酶原的细胞。而壁细胞在同基因寄主肾包膜下培养，也未分化。因此，我们得出结论：(1)表面黏液细胞在没有任何诱导因子的情况下自主分化；(2)黏液颈细胞和主细胞的分化需要间充质；(3)壁细胞的分化需要其他诱导因子（如神经刺激）。肝细胞生长因子（HGF）在腺胃中的作用：我们之前报道过，在原代培养中，HGF区域特异性刺激胃肠道上皮生长，并证实HGF介导腺胃上皮-间质相互作用。我们在发育中的腺胃中检测了HGF及其受体的表达。定量RT-PCR结果显示，HGF及其受体的表达在妊娠17-18天最高，此时上皮由层状上皮转变为单腺上皮，表明HGF控制上皮形态发生。HGF激活剂（HGF activator， HGFA）对HGF的激活：最近有报道称，HGF是由间质以无活性的前形式分泌的，在HGFA的作用下被激活。对发育中的胃肠道中HGFA的表达检测显示，HGFA仅在上皮细胞中表达，而在间质中不表达，在结肠中表达量高，在小肠和腺胃中表达量中等，在前胃中表达量少。

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.