鼻息肉是以Th2炎症反应为特征的疾病，鼻黏膜上皮细胞重塑是鼻息肉重要的病理特征，但其发生机制仍不明确。在鼻息肉上皮中，基底细胞和杯状细胞增生，纤毛细胞数目减少。我们研究发现15LO1在鼻息肉上皮细胞中表达显著升高，IL-13诱导鼻上皮细胞合成15LO1及代谢产物15-HETE-PE，15LO1和15-HETE-PE通过激活ERK通路促进鼻上皮基底细胞的分化，在支气管上皮细胞中15-HETE-PE能够调控杯状细胞分化。因此我们提出实验假说：在鼻息肉上皮细胞中，IL-13诱导上皮细胞中15LO1和15-HETE-PE表达升高，高表达的15LO1和15-HETE-PE通过ERK通路调控不同亚型上皮细胞分化过程。本项目通过体外培养原代鼻上皮细胞并对15LO1以及ERK通路进行阻断，探究15LO1和15-HETE-PE对不同亚型上皮细胞分化的调控作用，为逆转上皮细胞重塑提供治疗靶点。

Chronic rhinosinusitis with nasal polyp (CRSwNP) is often characterized by type 2 inflammation. It is well documented that nasal epithelial cell (NEC) remodeling is associated with CRSwNP, however, the mechanisms are still unclear. Previous studies reported histomorphological features of nasal polyps including aberrant basal cell and goblet cell proliferation and loss of ciliated cells. Our recent data showed that 15-lipoxygenase 1 (15LO1) expression is increased in NECs from patients with CRSwNP, IL-13 induces 15LO1 and 15-HETE-PE expression in vitro. 15LO1 and 15-HETE-PE promote basal cell differentiation by activating ERK pathway in NECs. Previous study reported 15-HETE-PE regulates goblet cell differentiation in human bronchial epithelial cells. Based on these studies, we hypothesized that in nasal polyps, Th2 inflammation cytokine induced 15LO1 and 15-HETE-PE production. Elevated 15LO1 and 15-HETE-PE modulate subtypes of nasal epithelial cell differentiation via ERK activation. Accordingly, primary NECs from both CRSwNP patients and healthy control subjects obtained from nasal brushings were cultured under an air-liquid interface system with or without 15LO1 siRNA and ERK pathway inhibitor. We sought to determine whether 15LO1 and 15-HETE-PE regulates cell differentiation and the pothetial mechanism. Together, this study strongly supports 15LO1 as a potential therapeutic target with the potential to inhibit nasal epithelial cells remodeling in patients with CRSwNP.