流行病学发现PM2.5母源性暴露与子代呼吸系统疾病发生密切相关，我们发现广州PM2.5母源性暴露引起的子代肺泡上皮细胞炎性损伤为仔鼠肺功能降低的主要原因之一，但机制不清。HMGB1作为新的致炎因子可与Toll 样受体结合激活NF-κB介导炎症反应，而PTEN可介导HMGB1诱发的TLR4激活。我们推测“PM2.5母源性暴露通过HMGB1引起PTEN活化促使TLR4-NF-κB 激活，诱发肺泡上皮细胞炎性损伤，启动肺部炎症的发生从而引起子代肺功能下降”是PM2.5母源性暴露致子代肺发育毒性的机制之一。本项目拟应用干细胞定向分化、Western blot、RNAi等技术分析PM2.5母源性暴露后子代肺泡上皮细胞HMGB1-PTEN-TLR4通路与炎性损伤的关系，从整体-细胞-分子三个层面揭示PM2.5母源性暴露致子代肺功能下降的机制，对深入理解母体环境与子代肺发育间的关系具有重要意义。

Epidemiological investigation has related maternal PM2.5 exposure to offspring lung disease. We found that reduced lung function in newborn rats associated with alveolar epithelial cells inflammation lesion induced by maternal PM2.5 exposure from Guangzhou. However, the mechanism is not clear. HMGB1 as a new inflammatory factor can promote inflammation via Toll-like receptor-mediated NF-κB activation. PTEN is critical for triggering HMGB1-mediated TLR4 activation. We hypothesize that "PM2.5 maternal exposure increased HMGB1 and PTEN in the lung, then trigger TLR4-NF-κB pathway activation in alveolar epithelial cells, resulting in offspring alveolar epithelial inflammation".This may be toxicity mechanism of PM2.5 on lung development. Therefore we intend to apply oriented differentiation of stem cells, Western blot, and RNAi to confirme our speculation in whole - cell – molecular three level. This project will reveal toxicity mechanisms of PM2.5 maternal exposure and provide important theoretical significance to deeply understand the relationship between maternal environment and offspring development.