期刊
BIOENGINEERED
卷 13, 期 5, 页码 12985-12997出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2022.2079304
关键词
miR-155-5p; hypoxia-induced pulmonary arterial hypertension; PYGL; WGCNA
资金
- Science and Technology Innovation Project of Shaoxing Health and Family Planning [2017CX010]
The miR-155-5p/PYGL pathway plays a crucial role in pulmonary arterial hypertension (PAH). Increased levels of miR-155-5p enhance cell proliferation, migration, and cell cycle progression in hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) by directly targeting PYGL.
Pulmonary arterial hypertension (PAH) is a cardiovascular disease that has high incidence and causes massive deaths. miR-155-5p/PYGL pathway was revealed to play a crucial role in PAH by weighted gene co-expression network analysis (WGCNA). The potential mechanism of miR-155-5p in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was analyzed through in vitro experiments. Hypoxia treatment stimulated the proliferation of PASMCs and increased the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1 alpha). At the same time, revealed by qRT-PCR and western blot, the level of miR-155-5p was raised, and the level of PYGL was decreased in hypoxia-induced PASMCs. Through CCK-8 assay, transwell assay and flow cytometry, it was revealed that miR-155-5p inhibitor remarkably inhibited the cell proliferation and migration and decreased the proportion of hypoxia-stimulated PASMCs in S and G2/M phases. Dual-luciferase reporter system was subsequently applied to validate the straight regulation of miR-155-5p on PYGL based on the analysis of online database. Furthermore, siPYGL was revealed to reverse the influence of miR-155-5p inhibitor on hypoxia-induced PASMCs. These outcomes indicate that the increased level of miR-155-5p in hypoxia-stimulated PASMCs could enhance the cell proliferation, cell migration, and cell cycle progression by targeting PYGL directly. This study may supply novel treatment strategies for PAH.
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