| http://purl.uniprot.org/citations/29913136 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29913136 | http://www.w3.org/2000/01/rdf-schema#comment | "Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are the predominant gelatinases in the developing lung. Studies have shown that the expression of MMP-2 and MMP-9 is upregulated in hypoxic fibroblasts, 15-hydroxyeicosatetraenoic acid (15-HETE) regulated fibroblasts migration via modulating MMP-2 or MMP-9, and that hypoxia/15-HETE is a predominant contributor to the development of pulmonary arterial hypertension (PAH) through increased angiogenesis. However, the roles of MMP-2 and MMP-9 in pulmonary arterial endothelial cells (PAECs) angiogenesis as well as the molecular mechanism of hypoxia-regulated MMP-2 and MMP-9 expression have not been identified. The aim of this study was to investigate the role of MMP-2 and MMP-9 in PAEC proliferation and vascular angiogenesis and to determine the effects of hypoxia-induced 15-HETE on the expression of MMP-2 and MMP-9. Western blot, immunofluorescence, and real-time PCR were used to measure the expression of MMP-2 and MMP-9 in hypoxic PAECs. Immunohistochemical staining, flow cytometry, and tube formation as well as cell proliferation, viability, scratch-wound, and Boyden chamber migration assays were used to identify the roles and relationships between MMP-2, MMP-9, and 15-HETE in hypoxic PAECs. We found that hypoxia increased MMP-2 and MMP-9 expression in pulmonary artery endothelium both in vivo and in vitro in a time-dependent pattern. Moreover, administration of the MMP-2 and MMP-9 inhibitor MMI-166 significantly reversed hypoxia-induced increases in right ventricular systemic pressure (RVSP), right ventricular function, and thickening of the tunica media. Furthermore, up-regulation of MMP-2 and MMP-9 expression was induced by 15-HETE, which regulates PAEC proliferation, migration, and cell cycle transition that eventually leads to angiogenesis. Our study demonstrated that hypoxia increases the expression of MMP-2 and MMP-9 through the 15-lipoxygenase/15-HETE pathway, and that MMP-2 and MMP-9 promote PAEC angiogenesis. These findings suggest that MMP-2 and MMP-9 may serve as new potential therapeutic targets for the treatment of PAH."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.yjmcc.2018.06.006"xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Chen H."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Dong Y."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Li G."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Zhu D."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Yan L."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/author | "Du W."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/name | "J Mol Cell Cardiol"xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/pages | "36-50"xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/title | "MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells."xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://purl.uniprot.org/core/volume | "121"xsd:string |
| http://purl.uniprot.org/citations/29913136 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29913136 |
| http://purl.uniprot.org/citations/29913136 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29913136 |
| http://purl.uniprot.org/uniprot/#_A2CF88-mappedCitation-29913136 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29913136 |
| http://purl.uniprot.org/uniprot/#_A2A5K8-mappedCitation-29913136 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29913136 |
| http://purl.uniprot.org/uniprot/#_A0A1B0GS88-mappedCitation-29913136 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29913136 |
| http://purl.uniprot.org/uniprot/#_P41245-mappedCitation-29913136 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29913136 |