State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Cardiac Surgery, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Respir Res. 2023 Aug 19;24(1):204. doi: 10.1186/s12931-023-02498-z.
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.
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.
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.
Augmented PLK1 is essential for the development of PH and is a druggable target for PH.
肺动脉高压（PH）是一种致命的血管疾病，治疗选择有限。肺泡缺氧与 PH 之间的机制联系尚不清楚。本研究旨在探讨有丝分裂调节蛋白 Polo 样激酶 1（PLK1）在 PH 发展中的作用。
使用小鼠肺以及人肺动脉平滑肌细胞和内皮细胞来研究缺氧对 PLK1 的影响。应用缺氧或 Sugen5416/缺氧诱导小鼠 PH。检查 Plk1 杂合子敲除小鼠和 PLK1 抑制剂（BI 2536 和 BI 6727）治疗的小鼠中 PLK1 在 PH 发展中的重要性。
缺氧通过诱导 HIF1α 和 RELA 来刺激 PLK1 的表达。Plk1 杂合子缺失的小鼠对缺氧诱导的 PH 有部分抗性。PLK1 抑制剂可改善小鼠 PH。
增强的 PLK1 对于 PH 的发展是必不可少的，并且是 PH 的可治疗靶点。
