RNA结合蛋白HuR通过GRSF1调节自噬相关基因Atg16l1在IBD发病中的机制研究

炎症性肠病（IBD）是一种病因不明的慢性炎症性疾病，其发病可能与肠上皮细胞中自噬降低相关。自噬相关基因Atg16l1影响克罗恩病的遗传易感性及预后，并参与控制炎症。调节Atg16l1或可成为IBD的有效治疗措施，因此深入研究其转录后调节机制十分必要，但目前此类研究尚匮乏。我们的研究发现IBD患者肠黏膜中ATG16L1蛋白及RNA结合蛋白GRSF1显著降低，并发现了在细胞水平敲减RNA结合蛋白GRSF1可下调ATG16L1。更有趣的是，我们发现，GRSF1的调节作用受到另一个RNA结合蛋白HuR的影响。因此，我们提出假设：RNA结合蛋白HuR可通过GRSF1在转录后水平调节Atg16l1的表达，从而影响IBD病理过程。该研究拟从转录后调节层面深入阐明RNA结合蛋白HuR通过GRSF1调节Atg16l1在IBD发病过程中的作用，为调控自噬、控制炎症治疗IBD提供理论依据。

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder of the intestine and is reported to associate with decreased autophagy activity in intestinal epithelial cells (IECs). Autophagy-related gene Atg16l1 is demonstrated to influence the risk to develop CD, and play a critical role in the prognosis of CD. In addition, Atg16l1 is involved in modulation of inflammation. Modulation of autophagy activity may be a therapeutic option for IBD, so it is essential to investigate the mechanism of Atg16l1 regulation. However, research focusing on Atg16l1 modulation is still limited. We found that ATG16L1 and RNA binding protein (RBP) GRSF1 were reduced significantly in intestinal mucosa of IBD patients. Our preliminary data showed that GRSF1 can regulate Atg16l1 in vitro. More interestingly, the regulatory role of GRSF1 could be subjected to the expression of another RBP HuR. Therefore, we hypothesize a novel pathway of HuR-GRSF1-Atg16l1 plays a key role through post-transcriptional gene regulation in the pathogenesis and development of IBD and will provide a solid theoretical basis for modulating autophagy activity as a potential IBD treatment.