Year: 2023
Type: article
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.
Source: Respiratory Research
Authors: 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
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, Wuhan Union Hospital, Huazhong University of Science and Technology, Capital Medical University, State Key Laboratory of Molecular Oncology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W4386001920