LIGHT在PM2.5暴露加剧哮喘气道重塑中的作用及机制研究

Airway remodelling is a characteristic feature of asthma. PM2.5 exposure would exacerbate airway remodeling in asthma, however, the mechanisms remain obscure. It has been recently reported that LIGHT played an important role in the pathophysiological process of airway remodeling in asthma. Our previous study indicated that the Beijing winter PM2.5 exposure could up-regulate the LIGHT levels of lung in asthmatic mouse, accompanying by significantly exacerbated airway remodeling. The findings in cell levels showed that LIGHT could promote the proliferation of smooth muscle cells, which is a typical feature of airway remodeling. Based on the above results, the scientific hypothesis we proposed is that PM2.5 exposure significantly exacerbated asthmatic airway remodeling by inducing LIGHT up-regulation. Therefore We intended to clarify the following issues as: 1) The role of LIGHT in the exacerbation of asthmatic airway remodeling by PM2.5 exposure; 2) The molecular mechanisms of LIGHT up-regulation by PM2.5 exposure; 3) The molecular mechanisms of LIGHT-mediated airway remodeling. So we can provide new targets for treatment of asthma patients and the intervention strategies for asthma crowd under PM2.5 exposure.

气道重塑是哮喘典型的病理特征，PM2.5暴露会导致哮喘气道重塑加重，然而机制不详。近来发现LIGHT在哮喘气道重塑中扮演重要角色，我们研究发现北京地区冬季PM2.5暴露可以诱导哮喘小鼠肺组织LIGHT明显升高，同时伴随有哮喘气道重塑的明显加剧，细胞水平研究发现LIGHT可促进平滑肌细胞的增殖，后者是气道重塑的标志之一。基于上述研究结果我们提出的科学假设是PM2.5暴露通过诱导LIGHT明显升高加剧了哮喘的气道重塑。针对上述科学假设我们拟通过分子生物学、细胞生物学，免疫组织化学等技术，在动物及细胞水平阐明1）LIGHT在PM2.5暴露加剧哮喘气道重塑中的作用；2）PM2.5上调LIGHT表达的分子机制；3）LIGHT介导气道重塑效应的分子机制。通过上述科学问题的解答为哮喘人群的干预治疗提供新的靶点，为PM2.5暴露下哮喘人群的防控干预策略提供依据。