Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
Eur J Pharmacol. 2019 Oct 5;860:172588. doi: 10.1016/j.ejphar.2019.172588. Epub 2019 Aug 1.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that often occurs in preterm infants. However, there is still no effective treatment for BPD. Recent studies demonstrated that connective tissue growth factor (CTGF) is involved in the development of BPD in experimental models. CTGF, also known as CCN2, is the second member of the CCN family and is necessary for normal lung development. The expression of CTGF is increased in lung tissues in infants with BPD. Hyperoxia, inflammation and mechanic ventilation increase CTGF expression which may promote fibroblast proliferation, matrix production and vascular remodeling. Conditional overexpression of CTGF in alveolar epithelial type II cells disrupts alveolarization and vascular development, induces vascular remodeling, and results in pulmonary hypertension, the pathological hallmarks of severe BPD. Further studies have shown that inhibition of CTGF by a CTGF monoclonal antibody improved alveolarization and vascular development, and decreased pulmonary vascular remodeling and pulmonary hypertension in a rodent model of BPD induced by hyperoxia. CTGF may be a novel target for BPD therapy in preterm infants.
支气管肺发育不良（BPD）是一种常发生于早产儿的慢性肺部疾病。然而，目前仍没有治疗 BPD 的有效方法。最近的研究表明，结缔组织生长因子（CTGF）参与了实验模型中 BPD 的发生发展。CTGF 也被称为 CCN2，是 CCN 家族的第二个成员，对于正常的肺发育是必需的。在患有 BPD 的婴儿的肺组织中，CTGF 的表达增加。高氧、炎症和机械通气增加 CTGF 的表达，这可能促进成纤维细胞增殖、基质产生和血管重塑。CTGF 在肺泡上皮细胞 II 型细胞中的条件性过表达破坏了肺泡化和血管发育，诱导血管重塑，并导致肺动脉高压，这是严重 BPD 的病理特征。进一步的研究表明，用 CTGF 单克隆抗体抑制 CTGF 可改善高氧诱导的 BPD 啮齿动物模型中的肺泡化和血管发育，并减少肺血管重塑和肺动脉高压。CTGF 可能是治疗早产儿 BPD 的一个新靶点。
