Ratineau C, Plateroti M, Dumortier J, Blanc M, Kédinger M, Chayvialle J A, Roche C
INSERM Unité 45, Hôpital Edouard Herriot, Lyon, France.
Differentiation. 1997 Dec;62(3):139-47. doi: 10.1046/j.1432-0436.1997.6230139.x.
The intestinal epithelium consists of enterocytes, endocrine cells, goblet cells and Paneth cells, which differentiate from pluripotent stem cells located at the crypt bases. The role of the epithelial-mesenchymal inter-actions has been well documented for the differentiation of enterocytes, but the mechanisms that control endocrine cell differentiation are poorly understood. We have cultured the intestinal endocrine cell line STC-1, which synthesizes most of the intestinal peptide hormones, in media conditioned by several subepithelial fibroblast cell lines from three distinct sites of intestine. The fibroblast Swiss 3T3 cell line was used as a non-intestinal control. Our results show that culture media from intestinal fibroblasts inhibit the proliferation rate of STC-1 cells, while those from Swiss 3T3 fibroblasts do not. As regards peptide hormone gene expression, Swiss 3T3-conditioned media have no effect, whereas media from intestinal fibroblasts variably affect cholecystokinin, glucagon, secretin and somatostatin mRNA levels. In particular, clonal subepithelial myofibroblasts do not exert the same effects as mixed subepithelial fibroblasts from homologous intestinal segment. Taken together, these results suggest that cultured fibroblasts of intestinal origin release soluble factors that inhibit STC-1 cell proliferation and modulate, in a region-specific manner, the expression of hormonal peptide genes in this nonspecialized endocrine cell line.
肠上皮由肠细胞、内分泌细胞、杯状细胞和潘氏细胞组成，这些细胞由位于隐窝底部的多能干细胞分化而来。上皮-间充质相互作用在肠细胞分化中的作用已有充分记载，但控制内分泌细胞分化的机制仍知之甚少。我们用来自肠道三个不同部位的几种上皮下成纤维细胞系条件培养基培养了合成大多数肠道肽类激素的肠道内分泌细胞系STC-1。成纤维细胞系Swiss 3T3用作非肠道对照。我们的结果表明，肠道成纤维细胞的培养基可抑制STC-1细胞的增殖速率，而Swiss 3T3成纤维细胞的培养基则无此作用。关于肽类激素基因表达，Swiss 3T3条件培养基没有影响，而肠道成纤维细胞的培养基可不同程度地影响胆囊收缩素、胰高血糖素、促胰液素和生长抑素的mRNA水平。特别是，克隆性上皮下肌成纤维细胞与来自同源肠段的混合上皮下成纤维细胞发挥的作用不同。综上所述，这些结果表明，源自肠道的培养成纤维细胞释放可溶性因子，这些因子可抑制STC-1细胞增殖，并以区域特异性方式调节该非特异性内分泌细胞系中激素肽基因的表达。
