miR-124/EGFR信号调控胰腺祖细胞增殖机制研究

项目名称： miR-124/EGFR信号调控胰腺祖细胞增殖机制研究

项目编号： No.31472159

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 滕春波

作者单位： 东北林业大学

项目金额： 86万元

中文摘要： 胰岛β细胞缺失或功能障碍会引起动物和人类糖尿病，利用胰腺祖细胞大量扩增分化产生功能性胰岛为糖尿病治疗提供了一条可行方案。探索胰腺祖细胞增殖条件及机制可为利用干细胞治疗糖尿病准备条件。前期工作中我们发现，在有或无血清培养基中添加EGF都能促进小鼠胰腺祖细胞增殖，无血清培养但去除EGF导致增殖停滞；在EGF存在条件下，miR-124过表达能显著抑制胰腺祖细胞增殖；对EGFR下游信号分析发现，miR-124能抑制AKT激活和ERK磷酸化，表明在胰腺祖细胞中存在miR-124与EGFR信号的交叉对话。本课题拟系统分析EGFR信号与miR-124在小鼠胰腺祖细胞增殖调控中的作用，解析 miR-124通过调控EGFR下游哪些信号分子影响胰腺祖细胞增殖，探索EGFR信号对miR-124是否存在反馈调节作用，从而进一步揭示胰腺发育中祖细胞增殖的分子机制，为利用胰腺祖细胞离体大量扩增治疗糖尿病打下基础。

中文关键词： 胰腺；祖细胞；增殖；小RNA；EGFR信号

英文摘要： Loss or dysfunction of insular β cells will cause diabetes in animals and human beings. Pancreatic progenitor cells, which can proliferate and differentiate into functional islets, provide a feasible scheme for diabetes treatment. Exploration of the mechanisms and conditions controlling the proliferation of pancreatic progenitors in vitro can provide clues for diabetes treatment. In our previous study, we have found that supplement of EGF in serum-containing or serum-free medium could significantly promote the proliferation of pancreatic progenitor cells, but deprivation of EGF from serum-free medium resulted in proliferation arrest. In EGF containing culture, overexpression of miR-124 significantly inhibited the proliferation of pancreatic progenitor cells and the activation of EGFR downstream signaling molecules, including AKT and ERK. Such results suggest that there is a crosstalk between miR-124 and EGFR signaling in the regulation of the proliferation of pancreatic progenitor cells. This subject will completely analyze the interaction between miR-124 and EGFR signaling in the control of the proliferation of pancreatic progenitors, reveal the signaling molecules of EGFR pathway targeted by miR-124, and explore whether there is feedback of EGFR signaling on miR-124 regulation in the pancreatic progenitor cells. We expect to uncover the regulation mechanism of the crosstalk between miR-124 and EGFR in progenitor cells during pancreatic development, and lay the foundation for the application of pancreatic progenitor cells in diabetes treatment.

英文关键词： pancreas;progenitor;proliferation;microRNA;EGFR signaling