miR-758-5p靶向phos-γH2A.X调控鼻息肉上皮细胞老化的机制

上皮细胞机械，免疫屏障功能的破坏是鼻息肉发病的重要因素。最新研究表明上皮细胞老化及老化相关分泌亚型如IL-6, IL-8, TNF-ɑ的释放在慢性炎症疾病中发挥重要作用。我们在前期的研究中发现鼻息肉上皮细胞老化及IL-6, IL-8, TNF-ɑ的分泌较对照组显著增加，说明上皮细胞老化可能参与了鼻息肉的发病，但具体调控机制尚不清楚。通过基因芯片筛选，我们发现miR-758-5p可能与鼻息肉上皮细胞的老化密切相关。因此，本课题拟研究miR-758-5p靶向phos-γH2A.X调控鼻息肉上皮细胞老化的机制。并且在人鼻息肉原代上皮细胞中沉默miR-758-5p，或在鼻息肉的模式鼠中鼻喷小鼠miR-758-5p拮抗剂，观察其对上皮细胞活性及IL-6, IL-8, TNF-ɑ分泌的影响，为鼻息肉的治疗提供新的思路和策略。

The destruction of physical and immune barrier function of epithelial cells，is an important factor in the pathogenesis of nasal polyps. Cell senescence and senescence-associated secretory phenotypes, such as IL-6, IL-8, TNF-ɑ, have been proved to exert important roles in chronic inflammatory diseases. In our previous studies, we found that compared to control group, nasal polyps showed increased epithelial senescent phenotypes and higher IL-6, IL-8, TNF-a secretion. Thus, senescence may play an important role in the pathogenesis of nasal polyps. However, the underlying regulatory mechanism is still not clear yet. According to miRNA microarrays analysis, we found that miR-758-5p was closely correlated with the senescence of epithelial cells in nasal polyps. Therefore, this study aims to explore the function of miR-758-5p targeting phos-γH2A.X regulating the senescence of epithelial cells and the secretion of IL-6, IL-8 and TNF-a, and its underlying mechanism. To observe how miR-758-5p affect the activity of epithelial cells and the secretion of IL-6, IL-8 and TNF-a, miR-758-5p will be silenced in primary epithelial cells of human nasal polyps. Furthermore, the murine miR-758-5p antagomir will be applied via nasal spray in mice model of nasal polyps. This study may provide a novel approach for the therapy of nasal polyps.