PDF(Pubmed)
Abstract：
Bronchopulmonary dysplasia (BPD) is a chronic lung disease characterized by retarded alveolarization. Tenascin-C (TN-C), an extracellular matrix glycoprotein and soluble molecule, is involved in tissue morphogenesis. In the present study, we demonstrated that the level of TN-C in lung tissues was greater in a mouse model of BPD induced by 85% oxygen. TN-C deficiency, however, impaired alveolarization in the hyperoxia-induced BPD model. In contrast, a functional TN-C blocking antibody ameliorated alveolar dysplasia in BPD-like mice. Mechanistically, hyperoxia increased the soluble TN-C (sTN-C) released from respiratory epithelial cells. On one hand, low-dose sTN-C promoted lung epithelial cell proliferation and migration, which was mediated by ICAM-1. On the other hand, high-dose sTN-C hindered the proliferation and migration of epithelial cells. Overall, this study revealed that TN-C plays a dual role in lung alveolarization and that TN-C may be a target in BPD therapy.
摘要：
支气管肺发育不良（BPD）是一种慢性肺部疾病，其特征是肺泡形成迟缓。生腱蛋白-C(TN-C),细胞外基质糖蛋白和可溶性分子，参与组织形态发生。在本研究中,我们证明，在85％氧气诱导的BPD小鼠模型中，肺组织中TN-C的水平更高。TN-C缺乏,然而,高氧诱导的BPD模型中的肺泡形成受损。相比之下,功能性TN-C阻断抗体改善BPD样小鼠的肺泡发育不良。机械上,高氧会增加呼吸道上皮细胞释放的可溶性TN-C（sTN-C）。一方面,低剂量sTN-C促进肺上皮细胞增殖和迁移，由ICAM-1介导。另一方面,高剂量sTN-C抑制了上皮细胞的增殖和迁移。总的来说,这项研究表明，TN-C在肺泡形成中起着双重作用，TN-C可能是BPD治疗的靶标。
