LncRNA MRAK028845在糖尿病小肠上皮干细胞异常分化的作用及机制

Diabetic enteropathy (DE) was previously regarded as a disease which had a connection with the abnormal motorial function of intestine, and the studies on its mechanism was fouced on the functional alterations of interstitial cells, such as Cajal cells. However, it could not explain the new discovery that intestinal barrier was impaired and epithelium was dysplastic in DE. In this study, we taken our pre-experiment results by LncRNA gene chip detection, which indicated MRAK028845 was upregulated in intestinal epithelial stem cells (IESC) of DM mice; MRAK028845 was correlated with Notch1/Hes1 signal pathway; We further found that MRAK028845 bound to Notch1 by RNA pull-down experiment. So we proposed the possible mechanisms that MRAK028845 promoted abnormal differentiation of IESC. We intend to further confirm that MRAK028845 directly binds to Notch1 and silences it, and explores the importance and significance of abnormal differentiation of IESC. This research may help to discover the new mechanism of differentiation of DM IESC, and provide new ideas and methods for the prevention and treatment of DE.

糖尿病肠病（DE）既往被认为与Cajal细胞功能改变所致的肠道运动功能异常有关。然而，近年来研究发现糖尿病(DM)肠上皮呈现增生异常，这些均难以用上述运动异常机制解释。通过预实验LncRNAs芯片发现MRAK028845在DM肠上皮干细胞（IESC）中显著高表达；相关性分析示MRAK028845与Notch1/Hes1通路相关；RNA pulldown筛选发现MRAK028845与Notch1相结合。由此我们提出MRAK028845促进IESC异常分化的可能机制，即DE时MRAK028845与Notch1结合并介导其沉默，从而导致IESC异常分化。本项目拟进一步证实MRAK028845与Notch1直接结合，并探讨这一事件对IESC异常分化的重要性和意义。本研究可能发现一种新的DM IESC分化异常的机制，为临床防治DE提供新的思路和方法。

糖尿病肠病（DE）既往被认为与Cajal细胞功能改变所致的肠道运动功能异常有关。然而，近年来研究发现糖尿病(DM)肠上皮呈现增生异常，这些均难以用上述运动异常机制解释。通过预实验LncRNAs芯片发现miR-380-5p在DM肠上皮干细胞（IESC）中显著高表达；相关性分析示miR-380-5p与Rspo3相关；生物信息学等方法筛选发现miR-380-5p与Rspo3相结合。由此我们提出miR-380-5p促进IESC异常分化的可能机制，即DE时miR-380-5p与Rspo3结合并介导其沉默，从而导致IESC异常分化。本项目拟进一步证实miR-380-5p与Rspo3直接结合，并探讨这一事件对IESC异常分化的重要性和意义。本研究可能发现一种新的DM IESC分化异常的机制，为临床防治DE提供新的思路和方法。