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- W2981612768 abstract "Background/aim: Hepatopulmonary syndrome (HPS) is a triad of advanced liver disease, intrapulmonary vasodilatation (IPVD), and arterial hypoxemia. Increasing evidence show HPS is associated with pulmonary microvascular hyperplasia. The aim of this work was to investigate the underlying mechanism of miR-145 in regulating the proliferation of pulmonary microvascular endothelial cells (PMVECs) and angiogenesis in HPS via PAI-1. Methods: Morphology score and number of pulmonary microvascular were assessed in lung tissues from rats with HPS by hematoxylin and eosin (H&E) staining. Expression levels of PAI-1 were assessed in lung tissues from HPS rats, as well as in PMVECs treated with HPS rat serum. We also selected the putative microRNA binding site on PAI-1 by bioinformatics analysis. Then, miR145-3p and miR145-5p expression levels in the lung and PMVECs of rats were detected by qRT-PCR because miR145-5p is a microRNA binding site on PAI-1. In addition, the effects of miR-145-5p regulation on PAI-1 were examined by upregulation and downregulation of miR-145-5p. And specific lentivirus transfection was used to overexpression and knockdown PAI-1 to assess PAI-1 function on PMVECs proliferation. Results: Our data showed that levels of PAI-1 expression in lung tissue of rats increased significantly when rats were treated with common bile duct ligation (CBDL). We found that levels of miR-145-5p were frequently downregulated in HPS tissues and cell lines, and overexpression of miR-145-5p dramatically inhibited PMVECs proliferation. We further verified PAI-1 as a novel and direct target of miR-145-5p in HPS. MiR-145-5p inhibits PAI-1 synthesis. And the expression changes of PAI-1 directly affect the proliferation of PMVECs. Conclusion: MiR-145-5p negatively regulates PMVECs proliferation through PAI-1 expression. In addition, overexpression of miR-145-5p may prove beneficial as a therapeutic strategy for HPS treatment." @default.
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- W2981612768 date "2019-01-01" @default.
- W2981612768 modified "2023-10-17" @default.
- W2981612768 title "MiR145-5p inhibits proliferation of PMVECs via PAI-1 in experimental hepatopulmonary syndrome rat pulmonary microvascular hyperplasia" @default.
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- W2981612768 doi "https://doi.org/10.1242/bio.044800" @default.
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