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Proliferation and differentiation of pancreatic cells, and their controlling mechanism in the course of development and regeneration

胰腺细胞增殖分化及其发育再生调控机制

基本信息

批准号：
11470008
负责人：
YAMASHINA Shohei
金额：
$ 8.26万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

1. Differentiation of exocrine and endocrine cells in the developing and regenerating rat pancreas: Immunohistochemical and in situ hybridization studies of pancreatic hormones indicated that regeneration of exocrine cells started on 2-3 days after the 90% pancreatectomy by the cell division of ductal cells, followed by completion at around 2 weeks. Neogenesis of endocrine cells also took place immediately after the pancreatectomy from the cells of intercalated duct and centroacinar cells. Glucagon cells appeared at first, from which insulin cells seemed to differentiate by non replicative process. The intercalated duct and centroacinar cells were suggested to be endocrine stem cells.PGP9.5, a well known neuronal marker, was disclosed to be an suitable immuno- histochemical marker of precursor and maturated endocrine cells in the process of development and regeneration.Three-dimensional analysis from serial sections indicated that all endocrine cells were developed under an intimate spatial relation with capillary.2. Contoling mechanism of endocrine differentiation: Anti PDX1 antibody was successfully prepared from cDNA, and analysis using the antibody was extensively undertaken in the process of development and regeneration of pancreas.3. Effect of CCK in the regeration of exocrine cells: Antagonist of CCK-1 receptor was demonstrated to inhibit the regeneration of exocrine cells after the pancreatectomy, suggesting that the proliferation of pancreatic tissue were controlled by CCK from duodenal tissue.4. Regenerated islet tissues were found to degenerate totally by 1 year after the partial pancreatectomy, and the process was confirmed to be non apoptotic cell death of the insulin cells.

1.大鼠胰腺发育和再生过程中外分泌和内分泌细胞的分化：胰腺激素免疫组织化学和原位杂交研究表明，胰腺切除后2-3天，胰腺外分泌细胞开始分裂，导管细胞分裂，约2周完成。胰腺切除后即刻可见内分泌细胞由间质管细胞和中央腺泡细胞分化而来。最早出现的是胰升糖素细胞，胰岛素细胞似乎是通过非复制过程分化的。结果：1.间质管和中央腺泡细胞可能是内分泌干细胞，PGP9.5是一个众所周知的神经元标记物，是发育和再生过程中前体细胞和成熟内分泌细胞的免疫组织化学标记物。内分泌分化调控机制：成功制备抗PDX1抗体，并广泛应用于胰腺的发育和再生过程中。CCK在外分泌细胞再生中的作用：CCK-1受体拮抗剂可抑制胰腺切除后外分泌细胞的再生，提示十二指肠组织CCK对胰腺组织的增殖有调控作用。胰腺部分切除后1年，再生的胰岛组织完全变性，证实为胰岛素细胞的非凋亡性死亡。