Search for cell growth factors produced in gastric epithelium

寻找胃上皮产生的细胞生长因子

• 批准号: 08457161
• 负责人: TATEMOTO Kazuhiko
• 金额: $ 4.48万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457161/
• 关键词: gastric epithelium; growth factor; biologically active peptide; differentiation-inducing factor; peptide isolation; orphan receptor; 構造決定; 分化誘導因子; 胃上皮癌; 生化学的解析; 蛋白質因子

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.

本建议的主要目的是确定细胞生长因子产生的胃上皮细胞和表征这些因素的生长或分化的上皮细胞的生理作用。从大鼠胃RGM- 1细胞的条件培养基中，我们已经分离并鉴定了IGF-Ⅱ，去胰岛素样生长因子-Ⅱ，IGF结合蛋白-2，β 2-微球蛋白，半胱氨酸蛋白酶抑制剂C，金属蛋白酶组织抑制剂-Ⅱ，使用生化谱方法。为了从胃上皮细胞中筛选具有生物活性的多肽，我们从牛胃中分离到一种新的肽，命名为apelin，它是G蛋白偶联受体APJ的内源性配体，由36个氨基酸残基组成，其前体由77个氨基酸残基组成。通过免疫组织化学技术已经在胃上皮中显示了含有爱帕琳的细胞。我们还发现，外周施用爱帕琳肽降低大鼠的血压。此外，我们已经表明，爱帕琳也在脂肪细胞中产生，这表明爱帕琳是，像瘦素，一种新的脂肪细胞来源的激素。我们一直在研究apelin对胃上皮细胞和脂肪细胞生长和分化的生理作用。

项目成果

Permert,J.: "Islet hormone secretion in pancreatic cancer patients with diabetes." Pancreas. 15. 60-68 (1997)

Permert,J.：“胰腺癌合并糖尿病患者的胰岛激素分泌。”

Kato,M.: "Hyperpolarization-activated Cl current elicited by pituitary adenylate cyclase activating polypeptide in Xenopus oocytes." Regulatory Peptides. 70. 167-172 (1997)

Kato,M.：“爪蟾卵母细胞中垂体腺苷酸环化酶激活多肽引起的超极化激活的 Cl 电流。”

Ma,H-T.: "Effects of pancreastatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells." Regulatory Peptides. 61. 143-148 (1996)

Ma，H-T.：“胰腺素和生长抑素对促分泌素诱导的单个大鼠胰岛细胞中细胞内游离钙升高的影响。”

Saito,Y.: "Bradykinin increases intracellular free Ca+ concentration and promotes insulin secretion in the clonal B-cell line,HIT-15 cells." Biochem. Biophys. Res. Commun.221. 577-580 (1996)

Saito, Y.：“缓激肽可增加细胞内游离 Ca 浓度并促进克隆 B 细胞系 HIT-15 细胞中的胰岛素分泌。”

Kogure,K.: "Uric acid changes in serum during different forms of hepatic inflow occlusion." Life Sci.60. 1781-1791 (1997)

Kogure,K.：“不同形式的肝流入闭塞期间血清中尿酸的变化。”