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Discovery of microv...
Discovery of microvascular miRNAs using public gene expression data : miR-145 is expressed in pericytes and is a regulator of Fli1
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- Larsson, Erik, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Wallenberglaboratoriet,Institute of Biomedicine,Wallenberg Laboratory
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- Fredlund Fuchs, Peder (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Heldin, Johan (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Barkefors, Irmeli (author)
- Uppsala universitet,Beräknings- och systembiologi
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- Bondjers, Cecilia, 1974 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Genové, Guillem (author)
- Karolinska Institutet
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Arrondel, Christelle (author)
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- Gerwins, Pär (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Kurschat, Christine (author)
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Schermer, Bernhard (author)
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Benzing, Thomas (author)
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Harvey, Scott J (author)
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- Kreuger, Johan (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Lindahl, Per, 1967 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Biomedicine,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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(creator_code:org_t)
- Springer Science and Business Media LLC, 2009
- 2009
- English.
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 1:11, s. 108-
- Related links:
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https://genomemedici...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- BACKGROUNDA function for the microRNA (miRNA) pathway in vascular development and angiogenesis has been firmly established. miRNAs with selective expression in the vasculature are attractive as possible targets in miRNA-based therapies. However, little is known about the expression of miRNAs in microvessels in vivo. Here, we identified candidate microvascular-selective miRNAs by screening public miRNA expression datasets.METHODSBioinformatics predictions of microvascular-selective expression were validated with real-time quantitative reverse transcription PCR on purified microvascular fragments from mouse. Pericyte expression was shown with in situ hybridization on tissue sections. Target sites were identified with 3' UTR luciferase assays, and migration was tested in a microfluid chemotaxis chamber.RESULTSmiR-145, miR-126, miR-24, and miR-23a were selectively expressed in microvascular fragments isolated from a range of tissues. In situ hybridization and analysis of Pdgfb retention motif mutant mice demonstrated predominant expression of miR-145 in pericytes. We identified the Ets transcription factor Friend leukemia virus integration 1 (Fli1) as a miR-145 target, and showed that elevated levels of miR-145 reduced migration of microvascular cells in response to growth factor gradients in vitro.CONCLUSIONSmiR-126, miR-24 and miR-23a are selectively expressed in microvascular endothelial cells in vivo, whereas miR-145 is expressed in pericytes. miR-145 targets the hematopoietic transcription factor Fli1 and blocks migration in response to growth factor gradients. Our findings have implications for vascular disease and provide necessary information for future drug design against miRNAs with selective expression in the microvasculature.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Larsson, Erik, 1 ...
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Fredlund Fuchs, ...
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Heldin, Johan
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Barkefors, Irmel ...
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Bondjers, Cecili ...
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Genové, Guillem
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Arrondel, Christ ...
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Gerwins, Pär
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Kurschat, Christ ...
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Schermer, Bernha ...
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Benzing, Thomas
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Harvey, Scott J
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Kreuger, Johan
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Lindahl, Per, 19 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Genome Medicine
- By the university
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Uppsala University
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University of Gothenburg
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Karolinska Institutet