miR-143通过下调ATG2B 抑制自噬诱发克罗恩病肠瘘的机制研究

Fistulae is a common complication of Crohn's disease (CD), often indicating the poor prognosis. At present, there are few researches on mechanism for intestinal fistulae complicated with CD. Our previous study found extension of tandem 3'UTR sequence in ATG2B, which was an important gene of autophagy, in fistulae tissue of patients with CD. As we know, ATG2B 3'UTR contains miR-143 binding sites. The study also found that the expression of miR-143 increased in intestinal fistulae tissue. Western Blotting confirmed down-expression of ATG2B and LC3 proteins in intestinal fisulae tissue compared to relatively normal tissue. So we postulate miR-143 may inhibit autophagy and induce intestinal fistulae complicated with CD by down-regulating ATG2B. We intend to detect expression of miR-143-3p, ATG2B and LC3 in intestinal fistulae tissue with CD, analysizing relationship with postoperative recurrence. Then miR-143 or ATG2B is regulated to detect the change of cell function including autophagy and apoptosis, which supports mechanisms of miR-143 regulating autophagy in CD fistulae. This study might help build the molecular regulation network in CD.

肠瘘是克罗恩病（CD）常见并发症，往往提示预后较差,而目前针对CD合并肠瘘的机制研究较少。我们前期研究发现，CD患者肠瘘组织中作为自噬重要的基因之一ATG2B串联重复3'UTR序列延长，而ATG2B 3'UTR包含miR-143的结合位点，同时发现瘘组织中miR-143的表达是升高的。Western Blotting进一步证实，肠瘘组织ATG2B和LC3蛋白的表达低于相对正常肠组织。因此推测，miR-143可能通过下调ATG2B抑制自噬，诱发CD肠瘘的发生。我们拟通过检测miR-143-3p、ATG2B和LC3在CD肠瘘组织的表达，结合临床数据分析其与术后复发的关系；在细胞水平上通过瞬时转染、慢病毒转染调控miR-143-3p或ATG2B，检测ATG2B和LC3的表达水平及细胞自噬、凋亡等功能改变，探讨miR-143调控自噬在CD肠瘘形成的机制，为进一步揭示CD的分子调控网络提供理论基础。

肠瘘是克罗恩病（CD）常见的并发症，往往提示预后较差,而目前针对CD合并肠瘘的机制研究较少。我们前期研究发现，CD患者肠瘘组织中作为自噬重要的基因之一ATG2B串联重复3'UTR序列延长，而ATG2B 3'UTR包含miR-143的结合位点，同时发现瘘组织中miR-143的表达是升高的。Western Blotting进一步证实，肠瘘组织ATG2B和LC3蛋白的表达低于相对正常肠组织。因此推测，miR-143可能通过下调ATG2B抑制自噬，诱发CD肠瘘的发生。在本项目的研究中，我们通过检测miR-143、ATG2B和LC3在CD肠瘘组织的表达，结合临床数据分析其与术后复发的关系；在细胞水平上通过瞬时转染、慢病毒转染调控miR-143或ATG2B，检测ATG2B和LC3的表达水平及细胞自噬、凋亡等功能改变，探讨了miR-143调控自噬在诱导CD炎症及其肠瘘形成的机制。本研究可为进一步揭示CD的分子调控网络提供理论基础。