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• W2966361102 endingPage "802" @default.
• W2966361102 startingPage "802" @default.
• W2966361102 abstract "Regulation of vascular smooth muscle cell (VSMC) proliferation is essential to maintain vascular homeostasis. Hypoxia induces abnormal proliferation of VSMCs and causes vascular proliferative disorders, such as pulmonary hypertension and atherosclerosis. As several cyclin/cyclin-dependent kinase (CDK) complexes and CDK inhibitors (CKIs) control cell proliferation, in this study, we investigated CKIs involved in the hypoxia-induced proliferation process of human primary pulmonary artery smooth muscle cells to understand the underlying molecular mechanism. We demonstrated that p15, p16, and p21 are downregulated in pulmonary artery smooth muscle cells when exposed to hypoxia. In addition, we identified novel hypoxia-induced microRNAs (hypoxamiRs) including miR-497, miR-1268a, and miR-665 that are upregulated under hypoxia and post-transcriptionally regulate p15, p16, and p21 genes, respectively, by directly targeting their 3'UTRs. These miRNAs promoted the proliferation of VSMCs, and their inhibition decreased VSMC proliferation even in hypoxic conditions. Overall, this study revealed that miRNA-mediated regulatory mechanism of CKIs is essential for hypoxia-induced proliferation of VSMCs. These findings provide insights for a better understanding of the pathogenesis of vascular proliferative disorders." @default.
• W2966361102 created "2019-08-13" @default.
• W2966361102 creator A5005030866 @default.
• W2966361102 creator A5028796996 @default.
• W2966361102 date "2019-07-31" @default.
• W2966361102 modified "2023-10-13" @default.
• W2966361102 title "Hypoxia Promotes Vascular Smooth Muscle Cell Proliferation through microRNA-Mediated Suppression of Cyclin-Dependent Kinase Inhibitors" @default.
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• W2966361102 doi "https://doi.org/10.3390/cells8080802" @default.
• W2966361102 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6721514" @default.
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• W2966361102 hasPublicationYear "2019" @default.
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