Respiratory Research (Aug 2023)
Polo-like kinase 1 promotes pulmonary hypertension
- Rongrong Chen,
- Hongfei Wang,
- Cuiting Zheng,
- Xiyu Zhang,
- Li Li,
- Shengwei Wang,
- Hongyu Chen,
- Jing Duan,
- Xian Zhou,
- Haiyong Peng,
- Jing Guo,
- Anchen Zhang,
- Feifei Li,
- Wang Wang,
- Yu Zhang,
- Jun Wang,
- Chen Wang,
- Yan Meng,
- Xinling Du,
- Hongbing Zhang
Affiliations
- Rongrong Chen
- 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
- Hongfei Wang
- Department of Cardiac Surgery, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Cuiting Zheng
- 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
- Xiyu Zhang
- Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University
- Li Li
- 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
- Shengwei Wang
- Department of Cardiac Surgery, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Hongyu Chen
- 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
- Jing Duan
- 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
- Xian Zhou
- 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
- Haiyong Peng
- 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
- Jing Guo
- 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
- Anchen Zhang
- Department of Cardiac Surgery, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Feifei Li
- Department of Cardiac Surgery, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Wang Wang
- Department of Physiology, Capital Medical University
- Yu Zhang
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Jun Wang
- Department of Physiology, Capital Medical University
- Chen Wang
- 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
- Yan Meng
- Department of Pathology, Beijing Lab for Cardiovascular Precision Medicine, Key Laboratory of Medical Engineering for Cardiovascular Disease, Capital Medical University
- Xinling Du
- Department of Cardiac Surgery, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Hongbing Zhang
- 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
- DOI
- https://doi.org/10.1186/s12931-023-02498-z
- Journal volume & issue
-
Vol. 24,
no. 1
pp. 1 – 16
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.
Keywords
