miR-148a在脂肪-胰岛信息交流中的作用及机制研究

肥胖是否会影响胰岛基因的表达知之甚少。我们通过二代测序发现，肥胖可以诱导胰岛细胞中miR-148a表达上调，同时伴随胰岛素基因表达的下降；后经软件预测结合双荧光素酶报告法发现miR-148a可以靶向胰岛素通路关键转录因子NeuroD1。据此推测miR-148a可能是脂肪-胰岛间信息交流的信号分子，在脂肪调控胰岛功能中发挥重要作用。本项目首先通过检验脂肪因子的变化，探明肥胖引起胰岛内miR-148a表达升高的诱因；然后利用Min6及β细胞特异性敲除miR-148a转基因小鼠，体内外探讨miR-148a对胰岛基因表达的调控作用；最后利用上述转基因小鼠的胰岛组织，通过转录组测序，鉴定miR-148a的靶基因谱，揭示miR-148a调控胰岛基因表达的作用机制。本研究将系统阐明miR-148a在脂肪调控胰岛功能中的作用及机制，为糖尿病的治疗提供新的靶点和思路。

Whether obesity affects the expression of islet genes is still unknown. By RNA-Seq, we found that obesity can induce miR-148a expression in pancreatic islet cells, accompanied by a decrease in expression of insulin gene. Software prediction combined with dual luciferase reporting revealed that miR-148a can target key transcription factor NeuroD1 of the insulin pathway. Based on this, it is speculated that miR-148a may be a signaling molecule for fatty tissue regulation of islet function. This project first examined the changes in adipokines to determine the cause of obesity-induced miR-148a expression in pancreatic islets. Next, miR-148a knockout in Min6 β-cell line and β-cell-specific transgenic mice was performed to explore the role of miR-148a on pancreatic islet gene expression. Finally, the pancreatic islet tissue of the transgenic mice described above was used to identify the target gene profile of miR-148a by transcriptome sequencing and reveal the mechanism of miR-148a regulation of pancreatic islet gene expression. This study will systematically elucidate the role and mechanism of miRNA-148a in fatty tissue regulation of islet function and provide new targets and ideas for the treatment of diabetes.