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10.1161/JAHA.117.007572 http://scihub22266oqcxt.onion/10.1161/JAHA.117.007572 C5907547!5907547 !29514810     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29514810 &cmd=llinks): Failed to open stream: HTTP request failed! 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Phosphatidylinositol 3-Kinase-DNA Methyltransferase 1-miR-1281-Histone Deacetylase 4 Regulatory Axis Mediates Platelet-Derived Growth Factor-Induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells |pdf=|usr=}}{{29514810 }} gab.com Text Phosphatidylinositol 3-Kinase-DNA Methyltransferase 1-miR-1281-Histone Deacetylase 4 Regulatory Axis Mediates Platelet-Derived Growth Factor-Induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells JO: J Am Heart Assoc http://www.kidney.de/pget.php?&tw=1&pmid=29514810 #FOAvip BACKGROUND: Platelet-derived growth factor BB, a potent mitogen of pulmonary artery smooth muscle cells (PASMCs), has been implicated in pulmonary arterial remodeling, which is a key pathogenic feature of pulmonary arterial hypertension. Previous microRNA profiling in platelet-derived growth factor BB-treated PASMCs found a significantly downregulated microRNA, miR-1281, but it has not been associated with any cellular function, and we investigated the possibility. METHODS AND RESULTS: Real-time quantitative reverse transcription-polymerase chain reaction assay proved that downregulation of miR-1281 was a conserved phenomenon in human and rat PASMCs. Overexpression and inhibition of miR-1281 in PASMCs promoted and suppressed, respectively, the cell proliferation and migration. Bioinformatic prediction and 3'-untranslated region reporter assay identified histone deacetylase 4 to be a direct target of miR-1281. Supporting this, proliferation and migration assay demonstrated the cellular function of histone deacetylase 4 is inversely correlated with that of miR-1281. Mechanistically, it is found that platelet-derived growth factor BB activates the phosphatidylinositol 3-kinase pathway, which then induces the expression of DNA methyltransferase 1, leading to enhanced methylation of a flanking CpG island and repressed miR-1281 expression. Finally, a reduced miR-1281 level was consistently identified in hypoxic PASMCs in vitro, in pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension, and in serum of patients with coronary heart disease-pulmonary arterial hypertension. These data suggest that there may be a diagnostic and therapeutic use for miR-1281. CONCLUSIONS: Herein, we report a novel regulatory axis, phosphatidylinositol 3-kinase-DNA methyltransferase 1-miR-1281-histone deacetylase 4, integrating multiple epigenetic regulators that participate in platelet-derived growth factor BB-stimulated PASMC proliferation and migration and pulmonary vascular remodeling. Twit Text FOAVip Phosphatidylinositol 3-Kinase-DNA Methyltransferase 1-miR-1281-Histone Deacetylase 4 Regulatory Axis Mediates Platelet-Derived Growth Factor-Induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells ????J Am Heart Assoc http://www.kidney.de/pget.php?&tw=1&pmid=29514810 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29514810 #FOAvip English Wikipedia <ref>{{Cite pmid|29514810 }}</ref> Phosphatidylinositol 3-Kinase-DNA Methyltransferase 1-miR-1281-Histone Deacetylase 4 Regulatory Axis Mediates Platelet-Derived Growth Factor-Induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells #MMPMID29514810 Li Y ; Li L ; Qian Z ; Lin B ; Chen J ; Luo Y ; Qu J ; Raj JU ; Gou D J Am Heart Assoc 2018[Mar]; 7 (6 ): ä PMID29514810 show ga BACKGROUND: Platelet-derived growth factor BB, a potent mitogen of pulmonary artery smooth muscle cells (PASMCs), has been implicated in pulmonary arterial remodeling, which is a key pathogenic feature of pulmonary arterial hypertension. Previous microRNA profiling in platelet-derived growth factor BB-treated PASMCs found a significantly downregulated microRNA, miR-1281, but it has not been associated with any cellular function, and we investigated the possibility. METHODS AND RESULTS: Real-time quantitative reverse transcription-polymerase chain reaction assay proved that downregulation of miR-1281 was a conserved phenomenon in human and rat PASMCs. Overexpression and inhibition of miR-1281 in PASMCs promoted and suppressed, respectively, the cell proliferation and migration. Bioinformatic prediction and 3'-untranslated region reporter assay identified histone deacetylase 4 to be a direct target of miR-1281. Supporting this, proliferation and migration assay demonstrated the cellular function of histone deacetylase 4 is inversely correlated with that of miR-1281. Mechanistically, it is found that platelet-derived growth factor BB activates the phosphatidylinositol 3-kinase pathway, which then induces the expression of DNA methyltransferase 1, leading to enhanced methylation of a flanking CpG island and repressed miR-1281 expression. Finally, a reduced miR-1281 level was consistently identified in hypoxic PASMCs in vitro, in pulmonary arteries of rats with monocrotaline-induced pulmonary arterial hypertension, and in serum of patients with coronary heart disease-pulmonary arterial hypertension. These data suggest that there may be a diagnostic and therapeutic use for miR-1281. CONCLUSIONS: Herein, we report a novel regulatory axis, phosphatidylinositol 3-kinase-DNA methyltransferase 1-miR-1281-histone deacetylase 4, integrating multiple epigenetic regulators that participate in platelet-derived growth factor BB-stimulated PASMC proliferation and migration and pulmonary vascular remodeling. |Animals [MESH] |Becaplermin/*pharmacology [MESH] |Cell Movement/*drug effects [MESH] |Cell Proliferation/*drug effects [MESH] |DNA (Cytosine-5-)-Methyltransferase 1/*metabolism [MESH] |Disease Models, Animal [MESH] |HEK293 Cells [MESH] |Histone Deacetylases/genetics/*metabolism [MESH] |Humans [MESH] |Hypertension, Pulmonary/*enzymology/genetics/pathology [MESH] |Male [MESH] |MicroRNAs/genetics/*metabolism [MESH] |Monocrotaline [MESH] |Muscle, Smooth, Vascular/*drug effects/enzymology/pathology [MESH] |Myocytes, Smooth Muscle/*drug effects/enzymology/pathology [MESH] |Phosphatidylinositol 3-Kinase/metabolism [MESH] |Pulmonary Artery/enzymology/pathology [MESH] |Rats, Sprague-Dawley [MESH] |Repressor Proteins/genetics/metabolism [MESH] |Signal Transduction/drug effects [MESH]Phosphatidylinositol 3-Kinase-DNA Methyltransferase 1-miR-1281-Histone(epmc).pdf DeepDyve Pubget Overpricing