Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Kunming Medical University, No. 295, Xichang Road, Wuhua District, Kunming, China.
Curr Allergy Asthma Rep. 2024 Oct 28;25(1):1. doi: 10.1007/s11882-024-01181-7.
Bone morphogenetic protein 2 (BMP2) belongs to the transforming growth factor-β (TGF-β) superfamily and plays an important role in regulating embryonic development, angiogenesis, osteogenic differentiation, tissue homeostasis, and cancer invasion. Increasing studies suggest BMP2 is involved in several respiratory diseases. This study aimed to review the role and mechanisms of BMP2 in respiratory diseases.
BMP2 signaling pathway includes the canonical and non-canonical signaling pathway. The canonical signaling pathway is the BMP2-SMAD pathway, and the non-canonical signaling pathway includes mitogen-activated protein kinase (MAPK) pathway and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. The BMP2 is related to pulmonary hypertension (PH), lung cancer, pulmonary fibrosis (PF), asthma, and chronic obstructive pulmonary disease (COPD). BMP2 inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), promotes the apoptosis of PASMCs to reduce pulmonary vascular remodeling in PH, which is closely related to the canonical and non-canonical pathway. In addition, BMP2 stimulates the proliferation and migration of cells to promote the occurrence, colonization, and metastasis of lung cancer through the canonical and the non-canonical pathway. Meanwhile, BMP2 exert anti-fibrotic function in PF through canonical signaling pathway. Moreover, BMP2 inhibits airway inflammation to maintain airway homeostasis in asthma. However, the signaling pathways involved in asthma are poorly understood. BMP2 inhibits the expression of ciliary protein and promotes squamous metaplasia of airway epithelial cells to accelerate the development of COPD. In conclusion, BMP2 may be a therapeutic target for several respiratory diseases.
目的综述：骨形态发生蛋白 2（BMP2）属于转化生长因子-β（TGF-β）超家族，在调节胚胎发育、血管生成、成骨分化、组织稳态和癌症侵袭等方面发挥着重要作用。越来越多的研究表明 BMP2 参与了几种呼吸系统疾病。本研究旨在综述 BMP2 在呼吸系统疾病中的作用及其机制。
最新发现：BMP2 信号通路包括经典信号通路和非经典信号通路。经典信号通路是 BMP2-SMAD 通路，而非经典信号通路包括丝裂原活化蛋白激酶（MAPK）通路和磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/AKT）通路。BMP2 与肺动脉高压（PH）、肺癌、肺纤维化（PF）、哮喘和慢性阻塞性肺疾病（COPD）有关。BMP2 抑制肺动脉平滑肌细胞（PASMCs）的增殖，促进 PASMCs 的凋亡，从而减少 PH 中的肺血管重塑，这与经典和非经典通路密切相关。此外，BMP2 通过经典和非经典通路刺激细胞的增殖和迁移，促进肺癌的发生、定植和转移。同时，BMP2 通过经典信号通路在 PF 中发挥抗纤维化作用。此外，BMP2 抑制气道炎症，维持哮喘中的气道稳态。然而，哮喘中涉及的信号通路仍知之甚少。BMP2 抑制纤毛蛋白的表达，促进气道上皮细胞的鳞状化生，从而加速 COPD 的发展。总之，BMP2 可能是几种呼吸系统疾病的治疗靶点。
