组织重塑相关miRNA与鼻息肉发生发展关系的研究

Management of patients with nasal polyp is still unsatisfactory and the underlying reason is the pathogenesis is far from clear. Our preliminary study demonstrated that there is difference in the inflammatory profiles of white and Asian patients with CRSwNP, and NP can be divided into subgroups according to the expression of inflammatory cytokines. So this indicated that if only studying the inflammatory factors, instead of gene regulation, it is impossible to understand the whole thing and essence of this disease. Therefore, we screened the NP using gene chip technique and found a group of miRNA which has significant difference expression in subgroups and is related to the tissue remodeling function. From this we concluded that this group of miRNA probably affect and regulate the development of NP. On the basis of previous works, we will further measure the expression and distribution of this group of miRNA in NP and investigate their function by established in vitro stimulation model. Thereby we can comprehensively and thoroughly illustrate the relationship between this group of miRNA and the development of NP. This project will explore the mechanism of the gene regulation of NP in a whole new perspective and provide the theoretical foundation for the treatment.

鼻息肉治疗效果不佳，根本原因在于其发病机理迄今为止仍不清楚。我们前期研究发现：鼻息肉的炎症类型存在着种族差异性，根据炎症因子的表达情况可将其分为不同的亚组。这就提示：如果仅限于研究鼻息肉的炎症因子，而不从上游，即从基因调控上进行研究，则不可能了解其发病的全貌和本质。鉴于此，我们采用基因芯片技术，对不同亚组鼻息肉进行筛查，结果发现了一族与组织重塑功能相关的miRNA,它们在不同亚组鼻息肉中均存在着明显的差异性表达。由此我们推断：很有可能正是由于这族与组织重塑相关的miRNA影响和调控了鼻息肉的发生发展。本课题将在此工作的基础上，进一步验证前期已筛选出的与组织重塑相关的miRNA，了解其在鼻息肉中的表达和分布情况；并利用已建立的鼻息肉体外刺激模型，了解其功能；从而全面深入地阐明这族组织重塑相关miRNA与鼻息肉发生、发展的关系，以期从全新的角度来探讨鼻息肉的基因调控机制并为其治疗提供新的靶点。

鼻息肉治疗效果不佳，根本原因在于其发病机理迄今为止仍不清楚。我们前期研究发现：鼻息肉的炎症类型存在着种族差异性，根据炎症因子的表达情况可将其分为不同的亚组。这就提示：如果仅限于研究鼻息肉的炎症因子，而不从上游，即从基因调控上进行研究，则不可能了解其发病的全貌和本质。鉴于此，我们采用基因芯片技术，对不同亚组鼻息肉进行筛查，结果发现了一族与组织重塑功能相关的miRNA,它们在不同亚组鼻息肉中均存在着明显的差异性表达。在通过实施qPCR及荧光原位杂交（FISH）验证后，我们发现：其中的miR-146a在鼻息肉及鼻腔粘膜上皮组织中的差异性表达。同时利用细胞培养、质粒转染技术发现在鼻腔粘膜上皮细胞中miR-146a对胃粘液素mucin5AC的负向调控，也更加提示miR-146a可以通过影响鼻腔粘膜黏液分泌，促使鼻息肉的组织重塑的发生发展。本研究发现并深入阐明了miR-146a对鼻息肉组织重塑基因调控机制的过程。