Mir-106b-5p Modulates Acute Pulmonary Embolism Via Nor1 In Pulmonary Artery Smooth Muscle Cells
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE(2020)
Abstract
Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR-106b-5p on APE was demonstrated in platelet-derived growth factor (PDGF)-induced PASMCs in vitro and in an APE-mouse model in vivo. The results showed that miR-106b-5p expression was downregulated in PDGF-induced PASMCs and APE mice, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR-106b-5p agomiR, and increased following treatment with miR-106b-5p antagomiR. miR-106b-5p targeted the 3 ' untranslated region of NOR-1 mRNA and reduced NOR1 expression. NOR1 overexpression reversed the effects of miR-106-5p on PDGF-induced PASMCs. The functional roles of miR-106b-5p in PDGF-induced PASMCs and an APE mouse-model, and the underlying molecular mechanisms were evaluated. AgomiR-106b-5p improved APE-induced mortality and pulmonary vascular proliferation in mice. These data suggest that miR-106-5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF-induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.
MoreTranslated text
Key words
acute pulmonary embolism, miR-106b-5p, pulmonary artery smooth muscle cells, NOR1, proliferation
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined