http://purl.uniprot.org/citations/24244514 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/24244514 | http://www.w3.org/2000/01/rdf-schema#comment | "Pulmonary hypertension (PH) is a serious disorder that causes significant morbidity and mortality. The pathogenesis of PH involves complex derangements in multiple pathways including reductions in peroxisome proliferator-activated receptor gamma (PPARγ). Hypoxia, a common PH stimulus, reduces PPARγ in experimental models. In contrast, activating PPARγ attenuates hypoxia-induced PH and endothelin 1 (ET-1) expression. To further explore mechanisms of hypoxia-induced PH and reductions in PPARγ, we examined the effects of hypoxia on selected microRNA (miRNA or miR) levels that might reduce PPARγ expression leading to increased ET-1 expression and PH. Our results demonstrate that exposure to hypoxia (10% O2) for 3-weeks increased levels of miR-27a and ET-1 in the lungs of C57BL/6 mice and reduced PPARγ levels. Hypoxia-induced increases in miR-27a were attenuated in mice treated with the PPARγ ligand, rosiglitazone (RSG, 10 mg/kg/d) by gavage for the final 10 d of exposure. In parallel studies, human pulmonary artery endothelial cells (HPAECs) were exposed to control (21% O2) or hypoxic (1% O2) conditions for 72 h. Hypoxia increased HPAEC proliferation, miR-27a and ET-1 expression, and reduced PPARγ expression. These alterations were attenuated by treatment with RSG (10 µM) during the last 24 h of hypoxia exposure. Overexpression of miR-27a or PPARγ knockdown increased HPAEC proliferation and ET-1 expression and decreased PPARγ levels, whereas these effects were reversed by miR-27a inhibition. Further, compared to lungs from littermate control mice, miR-27a levels were upregulated in lungs from endothelial-targeted PPARγ knockout (ePPARγ KO) mice. Knockdown of either SP1 or EGR1 was sufficient to significantly attenuate miR-27a expression in HPAECs. Collectively, these studies provide novel evidence that miR-27a and PPARγ mediate mutually repressive actions in hypoxic pulmonary vasculature and that targeting PPARγ may represent a novel therapeutic approach in PH to attenuate proliferative mediators that stimulate proliferation of pulmonary vascular cells."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0079503"xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Kang B.Y."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Park K.K."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Sutliff R.L."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Hart C.M."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Green D.E."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Bijli K.M."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/author | "Searles C.D."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/pages | "e79503"xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/title | "Hypoxia mediates mutual repression between microRNA-27a and PPARgamma in the pulmonary vasculature."xsd:string |
http://purl.uniprot.org/citations/24244514 | http://purl.uniprot.org/core/volume | "8"xsd:string |
http://purl.uniprot.org/citations/24244514 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24244514 |
http://purl.uniprot.org/citations/24244514 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24244514 |
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http://purl.uniprot.org/uniprot/P08047#attribution-58895B043A5555CB32453A5DABE13D82 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/24244514 |
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