Author:
Chen Rongrong,Wang Hongfei,Zheng Cuiting,Zhang Xiyu,Li Li,Wang Shengwei,Chen Hongyu,Duan Jing,Zhou Xian,Peng Haiyong,Guo Jing,Zhang Anchen,Li Feifei,Wang Wang,Zhang Yu,Wang Jun,Wang Chen,Meng Yan,Du Xinling,Zhang Hongbing
Abstract
Abstract
Background
Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development.
Methods
Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH.
Results
Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice.
Conclusions
Augmented PLK1 is essential for the development of PH and is a druggable target for PH.
Funder
the National Key R&D Program, Ministry of Science and Technology of China
Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献