Wnt5a inhibits hypoxia-induced pulmonary arterial smooth muscle cell proliferation by downregulation of beta-catenin

摘要

Chronic hypoxia-induced pulmonary arterial hypertension (HPH) is closely associated with profound vascular remodeling, especially pulmonary arterial medial hypertrophy and muscularization due to hyperplasia of pulmonary artery smooth muscle cells (PASMCs). Aberrant Wnt signaling has been associated with lung diseases, but its role in pulmonary hypertension is unclear. This study evaluated the effect of Wnt5a on hypoxia-induced proliferation of human PASMCs and its possible mechanism. The results show that hypoxia (3% O2, 48 h) induced proliferation of human PASMCs, accompanied with a significant decrease in Wnt5a gene expression, increase in beta-catenin and Cyclin Dl expression, as well as beta-eatenin nuclear translocation. Treatment with recombinant mouse Wnt5a significantly inhibited hypoxia-induced proliferation of human PASMCs, upregulation of Cyclin Dl and (3-catenin expression, as well as the nuclear translocation of (3-catenin. These effects were inhibited by Wnt5a antibody.