组织重塑是气道慢性炎症的主要病理特征，是决定慢性鼻-鼻窦炎（CRS）病变性质和预后的重要因素。IL-20亚家族调控JAK-STAT/ERK通路是介导组织重塑的关键，然其在上呼吸道炎症中的作用未见报道。我们前期研究发现IL-20亚家族主要成员IL-19及其受体IL-20R1/IL-20R2在以水肿、黏液化生和嗜酸性粒细胞（Eos）浸润为主要病理特征的CRS中高表达，并与细胞外基质调节因子MMP、Eos阳离子蛋白等表达相关。因此，本项目拟通过对鼻黏膜上皮细胞、成纤维细胞及鼻息肉组织块的培养，对比在IL-19激活与其受体封闭前后，JAK-STAT/ERK及TGF-β通路的活化差异，进一步分析上述通路对成纤维细胞合成纤维蛋白、胶原，鼻黏膜上皮细胞产生MMP及Eos趋化因子的作用，最终阐明IL-19及其受体调控水肿、黏液化生及Eos浸润的机制。为进一步完善CRS发病机制，寻找潜在治疗靶点提供理论依据

Tissue remodeling is the prominent pathophysiologic characteristic of chronic diseases of the airways. It is the key factor that affects the severity and prognosis of chronic rhinosinusitis (CRS). Recent studies indicate that the IL-20 subfamily promotes tissue remodeling. However, the roles of this subfamily in tissue remodeling of chronic airway diseases remain unclear. Our previous studies demonstrated that IL-19 and its receptors IL-20R1 and IL-20R2 are upregulated in CRS. This upregulation is found in the nasal mucosa characterized by nasal mucosa edema, mucinous metaplasia, and eosinophil infiltration, which contribute to increased levels of extracellular matrix regulator metalloproteinase (MMP)-7 and eosinophil cationic protein. The proposed study intends to detect the activations of JAK-STAT/ERK and TGF-β pathways in the primary nasal epithelial cells and to study the development of fibroblasts and nasal polyps in vitro after treatments with or without IL-19 stimulation. These findings will be used to determine the effects of activated JAK-STAT/ERK and inhibited TGF-β pathways on the expression of fibronectin and collagen in nasal fibroblasts and the expression of MMP, mucin, eotaxin and RANTES in the epithelial cells. Ultimately, the study aims to explain how the mechanism of IL-19 contributes to the imbalance of extracellular matrix, increased mucin deposition, and Eos infiltration during the tissue remodeling phase of CRS. The proposed study will elucidate the tissue remodeling mechanisms of CRS, provide a platform to develop new treatments for this disease.