极性蛋白Lgl介导的II型肺泡上皮细胞顶-底极性的丢失在肺纤维化发生中的作用及机制研究

II型肺泡上皮细胞的损伤与修复是肺纤维化发生的重要环节。上皮细胞的顶-底极性对维持细胞的正常生理功能具有重要作用，而细胞的极性丢失则与许多疾病密切相关。我们的前期研究证实“胸膜间皮细胞顶-底极性的丢失促进胸膜纤维化的发生”。我们的预实验提示抑制极性蛋白Lgl的过表达减轻小鼠肺纤维化的发生，博莱霉素作为纤维化的诱导物，导致了II型肺泡上皮细胞中Lgl表达上调及其顶-底极性的丢失，据此我们提出“细胞极性蛋白Lgl介导II型肺泡上皮细胞顶-底极性丢失参与肺纤维化发生”的假说。本项目拟进一步研究离体及在体条件下，II型肺泡上皮细胞受到致纤维化因子刺激后细胞顶-底极性的变化及其机制，并观察能否通过维持II型肺泡上皮细胞顶-底极性而抑制细胞增殖及胶原的过度生成，从而减轻肺纤维化。本项目提出了肺泡上皮细胞在介导肺纤维化发生中的新理念，并可为肺纤维化的防治提供新的靶点。

The damage and repair of type II alveolar epithelial cells play an important role in pulmonary fibrosis. Researches have shown that the apical-basal polarity of epithelial cells plays a vital role in maintaining normal functions of cell secretion, absorption and barrier protection, and loss of cell polarity is associated with many diseases. We previously found maintaining the pleural mesothelial cell polarity attenuates pleural fibrosis. In our preliminary experiments, we found inhibiting polarity protein Lgl expression can also attenuate pulmonary fibrosis. Bleomycin, as fibrosis inducer, leads to up-regulation of Lgl expression and loss of cell polarity in type II alveolar epithelial cells. Taken together, we hypothesized that Lgl-mediated apical-basal cell polarity loss in type II alveolar epithelial cells is involved in pulmonary fibrosis. On the basis, we will do experiments using cell and animal models to investigate the changes of cell polarity in type II alveolar epithelial cells induced by fibrogenic factors. We also investigate whether the proliferation and collagen expression can be reduced by maintaining the type II alveolar epithelial cell polarity. The project proposes a new concept of type II alveolar epithelial cells in pulmonary fibrosis, and provided a new target for the treatment of pulmonary fibrosis.