Huang Xi-Hui, Cheng Tao, Mou Ling, Bo Xin, Wei Xin-Ru
State Key Laboratory of Respiratory Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.
Shangrao People's Hospital, Shangrao 334000, China.
Sheng Li Xue Bao. 2023 Aug 25;75(4):515-520.
Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2 mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.
肺纤维化是一种严重的肺间质疾病，其特征在于肺组织结构破坏、成纤维细胞过度活化和增殖、大量细胞外基质（ECM）的分泌和积累以及肺功能受损。由于该疾病的复杂性，尚未建立合适的模拟人类肺纤维化的动物模型。近年来，精密肺切片（PCLS）已成为一种广泛用于研究肺生理学和发病机制的体外方法。该方法是一种介于器官和细胞水平之间的体外培养技术，因为它可以保留肺组织结构和肺组织中的各种气道细胞类型，模拟体内肺环境，并观察细胞与ECM之间的各种相互作用。因此，PCLS可以弥补其他模型（如细胞培养）的局限性。为了探究盘状结构域受体2（DDR2）在肺纤维化中的作用，成功构建了Ddr2小鼠。利用Cre-LoxP系统和PCLS技术验证小鼠PCLS中DDR2的缺失或敲低。转化生长因子β1（TGF-β1）可在体外诱导小鼠PCLS纤维化，可模拟肺纤维化的体内环境。在体外DDR2敲低-PCLS模型中，TGF-β1诱导的各种纤维化相关因子的表达显著降低，表明敲低DDR2可抑制肺纤维化的形成。这些结果为将DDR2作为肺纤维化治疗靶点的临床研究提供了新的视角。
