Up-regulation of cullin7 promotes proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension
Up-regulation of cullin7 promotes proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension
复制标题
cullin7上调促进缺氧肺动脉高压中肺动脉平滑肌细胞的增殖和迁移
DOI：
10.1016/j.ejphar.2019.172698
复制
发表时间：
2019
影响因子：
5
通讯作者：
Chang-Ping Hu
中科院分区：
文献类型：
--
作者：
Hong Liu;Xiao-Yue Ge;Ning Huang;Ting Liu;Mao-Zhong Yao;Zheng Zhang;Zhao-Xin Qian;Chang-Ping Hu
It has well been demonstrated that E3 ubiquitin ligase cullin7 plays important roles in cancer cell growth control via down-regulating p53 expression. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular remodeling. Therefore, whether cullin7 participates in hypoxia-induced pulmonary vascular remodeling deserves to be elucidated. The present study found that hypoxia up-regulated the expression of cullin7 mRNA and protein in pulmonary arteries and pulmonary artery smooth muscle cells, and knockdown of cullin7 inhibited hypoxia-induced proliferation and migration of pulmonary artery smooth muscle cells and reversed hypoxia-induced inhibition of p53 expression. Notably, administration of proteasome inhibitor MG132 significantly inhibited the expression of cullin7 and up-regulated the expression of p53 in pulmonary arteries concomitantly with improvement of hypoxia-induced pulmonary vascular remodeling. Our study demonstrated that hypoxia induced up-regulation of cullin7 expression resulting to the proliferation and migration of pulmonary artery smooth muscle cells via down-regulating p53 expression, which contributed to pulmonary vascular remodeling.
