机构：[1]Department of Cardiac surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China临床科室心脏外科中心首都医科大学附属安贞医院[2]School Of General Practice and Continuing Education, Capital Medical University, Beijing, China
OBJECTIVE: The aim of this study was to investigate the role of microRNA-593-5p (miR-593-5p) in hypoxia-induced pulmonary hypertension (HPH), and to explore its underlying mechanism. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were housed in a hypoxia environment 8 hours per day for consecutive 4 weeks. After the establishment of the HPH rat model, we detected the right ventricular systolic pressure (RVSP) and right heart hypertrophy index (RVHI) in HPH rats and controls. The expression levels of miR-593-5p and polo-like kinase 1 (PLK1) in rat lungs were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Subsequently. miR-593-5p mimics and inhibitor were constructed and transfected into cells. The proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) were accessed by cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The protein level of PLK1 in PASMCs after transfection with miR-593-5p mimics or inhibitor was detected by Western blot. Dual-luciferase reporter gene assay was conducted to verify the binding condition of miR-593-5p and PLK1. Finally, rescue experiments were performed to explore whether the regulatory effect of miR-593-5p on HPH development was associated with PLK1. RESULTS: RVSP and RVHI in rats of the hypoxic group were significantly higher than those of controls. MiR-593-5p was significantly downregulated while PLK1 was remarkably upregulated in lung tissues of HPH rats than those of controls. Similarly, miR-593-5p expression in PASMCs decreased gradually with the prolongation of hypoxia induction. Overexpression of miR-593-5p remarkably inhibited the proliferation and migration of PASMCs. Subsequently, dual-luciferase reporter gene verified the binding condition of miR-593-5p and PLK1. Both the mRNA and protein levels of PLK1 were negatively regulated by miR-593-5p. Also, rescue experiments demonstrated that the inhibitory effects of miR-593-5p on the proliferation and migration of PASMCs could be reversed by PLK1 overexpression. CONCLUSIONS: MiR-593-5p is lowly expressed in lung tissues of HPH rats. Meanwhile, it stimulates the proliferation and migration of PASMCs via targeting PLK1, thereby promoting HPH development.
第一作者机构：[1]Department of Cardiac surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Department of Cardiac surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Zhao T-F,Wang S-Y,Zou X-Z,et al.MiR-593-5p promotes the development of hypoxic-induced pulmonary hypertension via targeting PLK1[J].EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES.2019,23(8):3495-3502.doi:10.26355/eurrev_201904_17715.
APA：
Zhao, T-F,Wang, S-Y,Zou, X-Z&Zhao, H-D.(2019).MiR-593-5p promotes the development of hypoxic-induced pulmonary hypertension via targeting PLK1.EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES,23,(8)
MLA：
Zhao, T-F,et al."MiR-593-5p promotes the development of hypoxic-induced pulmonary hypertension via targeting PLK1".EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES 23..8(2019):3495-3502
