剪切起源的circRNA对气道黏蛋白MUC5AC调控在哮喘发病中的作用和机制研究

气道黏液高分泌是哮喘典型特征和致死原因之一，然而其高分泌的调控机制尚不明了。我们前期发现在哮喘患儿支气管肺泡灌洗液细胞和小鼠模型肺部hsa_circ_0000782表达上升。hsa_circ_0000782可通过miR-23b-3p/STAT6信号通路参与黏蛋白MUC5AC表达调控；且hsa_circ_0000782生成可能受剪切因子SRSF3调控。因此，推测SRSF3通过调节hsa_circ_0000782生成参与MUC5AC表达调控。我们拟在前期研究基础上，先验证哮喘中hsa_circ_0000782对气道MUC5AC表达的调控效应和机制；再利用SRSF3敲除小鼠和RNA干扰/过表达等技术，研究hsa_circ_0000782生成的调控和机制；最后探讨SRSF3和hsa_circ_0000782干预对哮喘黏液高分泌的防治作用，这将使我们深入理解哮喘发病机制，并为其防治提供新思路。

Airway mucus hypersecretion is a typical characteristic of asthma and one important causes of death. However, the accurate mechanism of airway mucus hypersecretion in asthma is still unclear. Our previous studies showed that circRNA hsa_circ_0000782 was upregulated in bronchoalveolar lavage fluid cells of children with asthma and mouse asthamtic model, not only in the interstitial cells and inflammatory cells, but also in the airway epithelial cells. Hsa_circ_0000782 regulated the mucous MUC5AC through the hsa-miR-23b-3p and STAT6 signalling pathway. Moreover, our research showed that the splicing and circularization of hsa_circ_0000782 may be regulated by splicing factor SRSF3. Hence, we speculate that splicing factor SRSF3 may regulated the expression of MUC5AC by affecting the biogenesis of hsa_circ_0000782 and followed signalling pathway in asthma. Based on our previous studies, we aim to verify the accurate mechanisms that hsa_circ_0000782 (mmu_circ_0003573, mouse-derived hsa_circ_0000782) regulates the MUC5AC expression in asthma. Then, to investigate the regulating effects and mechanisms of hsa_circ_0000782 by using conditional SRSF3 gene konckout mouse model and RNA knockdown/overexpression in bronchial epithelial cells. Finally, we investigate the possiblity of SRSF3 and mmu_circ_0003573 (hsa_circ_0000782) inhibitors in improving mucous hypersecretion of children with asthma. This study will bring a new insight into the mechanism, prevention and intervention of asthma.