肺泡II型上皮细胞RhoA/SLC26A4/TGF-β1信号轴在哮喘中的作用及机制研究

近年来随着环境污染加剧，哮喘的发病率逐年升高，已成为一项重大的全球性健康难题。肺泡II型上皮细胞作为肺内的结构细胞具有分泌表面活性蛋白、细胞因子和趋化因子及充当“干细胞”修复损伤肺组织的功能。我们在前期研究中发现肺泡II型上皮细胞RhoA敲除能够加重过敏原诱导的气道炎症反应和炎症因子TGF-β1的缺失。通过对小鼠原代肺泡II型上皮细胞进行RNA测序发现SLC26A4是RhoA的靶基因，并且基于数据库的生物信息学分析显示哮喘患者气道上皮细胞中SLC26A4和TGF-β1表达存在相关性。故我们提出“肺泡II型上皮细胞RhoA通过调控SLC26A4/TGF-β1信号轴参与过敏性哮喘的发病”的假说。本项目拟通过构建肺泡II型上皮细胞特异性基因敲除鼠、RNA测序等分子生物学方法，揭示RhoA/SLC26A4/TGF-β1信号通路促进哮喘炎症反应的新机制，为哮喘的预防和治疗提供新的理论基础和潜在靶点。

The incidence of asthma has been greatly increasing in the last decades under the background of deteriorating environment, and it has been a major global health problem. Type II alveolar epithelial cell, as a structural cell in the lung, has the function of secreting surfactant protein, cytokines and chemokines, and acting as a "progenitor" to repair damaged lung tissue. Our previous studies found that the absence of RhoA in type II alveolar epithelial cell could aggravate allergen-induced airway inflammation and result in loss of inflammatory factor TGF-β1. RNA-sequencing of the primary type II alveolar epithelial cell from mice showed SLC26A4 is possible target gene of RhoA, and bioinformatic analysis found a correlation between SLC26A4 and TGF-β1 in epithelium from asthmatics. Therefore, we raised the hypothesis that RhoA in type II alveolar epithelial cells participates the pathogenesis of allergic asthma through regulating the SLC26A4/TGF-β1 signal axis. This project intends to reveal the new mechanism of RhoA/SLC26A4/TGF-β1 signaling pathway to promote inflammatory response in asthma through construction of specific gene knockout in type II alveolar epithelial cells of mice, RNA sequencing and other molecular biological methods to provide novel theoretical basis and potential targets for the prevention and treatment of asthma.