PDF(Pubmed)
Abstract：
BACKGROUND: The PI3K/Akt/mTOR pathway and autophagy are important physiological processes. But their roles in eCRSwNP remains controversial.
METHODS: In this study, we used the eCRSwNP mouse model, PI3K/Akt/mTOR pathway inhibitors, and autophagy inhibitors and activators to investigate the regulatory effects of the PI3K/Akt/mTOR pathway on autophagy, and their effects on eosinophilic inflammation, and tissue remodeling. The role of ILC2s in eCRSwNP was also studied, and the relationship between ILC2s and autophagy was preliminarily determined.
RESULTS: Our results show that eosinophilic inflammation in eCRSwNP mice could be inhibited by promoting the autophagy; otherwise, eosinophilic inflammation could be promoted. Meanwhile, inhibition of the PI3K/Akt/mTOR pathway can further promote autophagy and inhibit eosinophilic inflammation. Meanwhile, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy can reduce the number of ILC2s and the severity of tissue remodeling in the nasal polyps of eCRSwNP mice.
CONCLUSIONS: We conclude that the PI3K/Akt/mTOR pathway plays roles in eosinophilic inflammation and tissue remodeling of eCRSwNP, in part by regulating the level of autophagy. The downregulation of autophagy is a pathogenesis of eCRSwNP; therefore, the recovery of normal autophagy levels might be a new target for eCRSwNP therapy. Furthermore, autophagy might inhibit eosinophilic inflammation and tissue remodeling, in part by reducing the number of ILC2s.
METHODS: In this study, we used the eCRSwNP mouse model, PI3K/Akt/mTOR pathway inhibitors, and autophagy inhibitors and activators to investigate the regulatory effects of the PI3K/Akt/mTOR pathway on autophagy, and their effects on eosinophilic inflammation, and tissue remodeling. The role of ILC2s in eCRSwNP was also studied, and the relationship between ILC2s and autophagy was preliminarily determined.
RESULTS: Our results show that eosinophilic inflammation in eCRSwNP mice could be inhibited by promoting the autophagy; otherwise, eosinophilic inflammation could be promoted. Meanwhile, inhibition of the PI3K/Akt/mTOR pathway can further promote autophagy and inhibit eosinophilic inflammation. Meanwhile, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy can reduce the number of ILC2s and the severity of tissue remodeling in the nasal polyps of eCRSwNP mice.
CONCLUSIONS: We conclude that the PI3K/Akt/mTOR pathway plays roles in eosinophilic inflammation and tissue remodeling of eCRSwNP, in part by regulating the level of autophagy. The downregulation of autophagy is a pathogenesis of eCRSwNP; therefore, the recovery of normal autophagy levels might be a new target for eCRSwNP therapy. Furthermore, autophagy might inhibit eosinophilic inflammation and tissue remodeling, in part by reducing the number of ILC2s.
摘要：
背景：PI3K/Akt/mTOR通路和自噬是重要的生理过程。但是它们在eCRSwNP中的作用仍然存在争议。
方法：在本研究中，我们使用了eCRSwNP小鼠模型，PI3K/Akt/mTOR通路抑制剂,以及自噬抑制剂和激活剂研究PI3K/Akt/mTOR通路对自噬的调节作用,以及它们对嗜酸性粒细胞炎症的影响，和组织重塑。还研究了ILC2s在eCRSwNP中的作用，初步确定了ILC2s与自噬的关系。
结果：我们的结果表明，通过促进自噬可以抑制eCRSwNP小鼠的嗜酸性炎症；否则，可促进嗜酸性粒细胞炎症。同时,抑制PI3K/Akt/mTOR通路可以进一步促进自噬和抑制嗜酸性粒细胞炎症。同时,抑制PI3K/Akt/mTOR通路和促进自噬可降低eCRSwNP小鼠鼻息肉组织重塑的程度和ILC2s的数量。
结论：我们得出结论，PI3K/Akt/mTOR通路在eCRSwNP的嗜酸性粒细胞炎症和组织重塑中起作用，部分通过调节自噬水平。自噬的下调是eCRSwNP的发病机制；因此，正常自噬水平的恢复可能是eCRSwNP治疗的新靶点.此外，自噬可能抑制嗜酸性粒细胞炎症和组织重塑，部分是通过减少ILC2的数量。
方法：在本研究中，我们使用了eCRSwNP小鼠模型，PI3K/Akt/mTOR通路抑制剂,以及自噬抑制剂和激活剂研究PI3K/Akt/mTOR通路对自噬的调节作用,以及它们对嗜酸性粒细胞炎症的影响，和组织重塑。还研究了ILC2s在eCRSwNP中的作用，初步确定了ILC2s与自噬的关系。
结果：我们的结果表明，通过促进自噬可以抑制eCRSwNP小鼠的嗜酸性炎症；否则，可促进嗜酸性粒细胞炎症。同时,抑制PI3K/Akt/mTOR通路可以进一步促进自噬和抑制嗜酸性粒细胞炎症。同时,抑制PI3K/Akt/mTOR通路和促进自噬可降低eCRSwNP小鼠鼻息肉组织重塑的程度和ILC2s的数量。
结论：我们得出结论，PI3K/Akt/mTOR通路在eCRSwNP的嗜酸性粒细胞炎症和组织重塑中起作用，部分通过调节自噬水平。自噬的下调是eCRSwNP的发病机制；因此，正常自噬水平的恢复可能是eCRSwNP治疗的新靶点.此外，自噬可能抑制嗜酸性粒细胞炎症和组织重塑，部分是通过减少ILC2的数量。
