Search for cell growth factors produced in gastric epithelium

这一建议的主要目的是鉴定胃上皮细胞产生的细胞生长因子，并表征这些因子在胃上皮细胞生长或分化中的生理作用。从大鼠胃RGM-1细胞条件培养液中分离鉴定了胰岛素样生长因子-II、DES-L-胰岛素样生长因子-II、胰岛素样生长因子结合蛋白-2、富含半胱氨酸的酸性分泌蛋白、β_2-微球蛋白、胱抑素C、金属蛋白酶组织抑制因子-II。这些结果表明这些蛋白因子可能在胃上皮细胞中发挥生理作用。为了从胃上皮细胞中鉴定生物活性多肽，我们从牛胃中分离出一种新的多肽，命名为apelin，作为孤儿G蛋白偶联受体APJ的内源性配体。免疫组织化学技术显示胃上皮细胞内含有apelin细胞。我们还发现，外周给药可降低大鼠的血压。此外，我们还发现在脂肪细胞中也产生了apelin，这表明apelin和瘦素一样，是一种新的脂肪细胞衍生激素。我们一直在研究apelin对胃上皮细胞和脂肪细胞生长或分化的生理作用。

The principal aim of this proposal is to identify cell growth factors produced in gastric epithelium and to characterize the physiological roles of these factors on growth or differentiation of the epithelium. From a conditioned medium of rat gastric RGM- 1 cells, we have isolated and identified IGF-II, des-l-IGF-II, IGF binding protein-2, SPARC (Secreted Protein Acidic and Rich in Cysteine), beta2-microglobulin, cystatin C, tissue inhibitor of metalloproteinases-II using a biochemical profile method. These results suggest that these protein factors may play physiological roles in gastric epithelium.In efforts to identify biological active peptides from gastric epithelium, we have isolated a novel peptide designated apelin from bovine stomach as an endogenous ligand for an orphan G-protein-coupled receptor APJ.Apelin have been found to consist 36 amino acid residues and its precursor 77 amino acid residues. Apelin containing cells have been shown in gastric epithelium by an immunohistochemical technique. We have also found that peripheral administration of apelin lowers blood pressure in rats. Furthermore, we have shown that apelin is also produced in the adipocytes, suggesting that apelin is, like leptin, a novel adipocyte-derived hormone. We have been studying the physiological roles of apelin on growth or differentiation of gastric epithelium and the adipocytes.