| An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension. | |
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MedLine Citation:
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PMID: 23263626 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling associated with obliteration of pulmonary arterioles and formation of plexiform lesions composed of hyperproliferative endothelial and vascular smooth-muscle cells. Here we describe a microRNA (miRNA)-dependent association between apelin (APLN) and fibroblast growth factor 2 (FGF2) signaling in pulmonary artery endothelial cells (PAECs). APLN deficiency in these cells led to increased expression of FGF2 and its receptor FGFR1 as a consequence of decreased expression of miR-424 and miR-503, which directly target FGF2 and FGFR1. miR-424 and miR-503 were downregulated in PAH, exerted antiproliferative effects in PAECs and inhibited the capacity of PAEC-conditioned medium to induce the proliferation of pulmonary artery smooth-muscle cells. Reconstitution of miR-424 and miR-503 in vivo ameliorated pulmonary hypertension in experimental models. These studies identify an APLN-dependent miRNA-FGF signaling axis needed for the maintenance of pulmonary vascular homeostasis. |
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Authors:
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Jongmin Kim; Yujung Kang; Yoko Kojima; Janet K Lighthouse; Xiaoyue Hu; Micheala A Aldred; Danielle L McLean; Hyekyung Park; Suzy A Comhair; Daniel M Greif; Serpil C Erzurum; Hyung J Chun |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-12-23 |
Journal Detail:
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Title: Nature medicine Volume: 19 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-08 Completed Date: 2013-03-06 Revised Date: 2013-05-08 |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
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Languages: eng Pagination: 74-82 Citation Subset: IM |
Affiliation:
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Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE42343 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Movement Cell Proliferation Cells, Cultured Culture Media, Conditioned / pharmacology Down-Regulation Endothelial Cells / metabolism Fibroblast Growth Factor 2 / biosynthesis, metabolism* Humans Hypertension, Pulmonary / genetics, metabolism*, pathology Intercellular Signaling Peptides and Proteins / metabolism* Mice Mice, Inbred C57BL Mice, Knockout MicroRNAs / genetics, metabolism* Muscle, Smooth, Vascular / metabolism, physiology Myocytes, Smooth Muscle / metabolism Pulmonary Artery / metabolism, pathology, physiopathology RNA Interference RNA, Small Interfering Rats Receptor, Fibroblast Growth Factor, Type 1 / biosynthesis Signal Transduction Vascular Diseases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL069170/HL/NHLBI NIH HHS; HL093362/HL/NHLBI NIH HHS; HL095654/HL/NHLBI NIH HHS; HL101284/HL/NHLBI NIH HHS; HL113005/HL/NHLBI NIH HHS; K08 HL093362/HL/NHLBI NIH HHS; K08 HL095654/HL/NHLBI NIH HHS; P30 HL101284/HL/NHLBI NIH HHS; R01 HL069170/HL/NHLBI NIH HHS; R01 HL113005/HL/NHLBI NIH HHS; UL1 TR000142/TR/NCATS NIH HHS; UL1 TR000439/TR/NCATS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/APLN protein, human; 0/Culture Media, Conditioned; 0/Intercellular Signaling Peptides and Proteins; 0/MIRN424 microrna, human; 0/MIRN503 microRNA, human; 0/MicroRNAs; 0/RNA, Small Interfering; 103107-01-3/Fibroblast Growth Factor 2; EC 2.7.10.1/FGFR1 protein, human; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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