| Diverging Alternative Splicing Fingerprints in TGFβ Signaling Pathway Identified in Thoracic Aortic Aneurysms. | |
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MedLine Citation:
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PMID: 21448509 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Impaired regulation of transforming growth factor-β (TGFβ) signaling pathway has been linked to thoracic aortic aneurysm (TAA). Previous work has indicated that differential splicing is a common phenomenon, potentially influencing the function of proteins. In the present study we have investigated the occurrence of differential splicing in the TGFβ pathway associated with TAA in patients with bicuspid (BAV) and tricuspid (TAV) aortic valve. Affymetrix Human Exon arrays have been applied on 81 intima/media tissue samples from dilated (n=51) and non-dilated (n=30) aortas of TAV and BAV patients. In order to analyze occurrence of alternative splicing in TGFβ pathway, multivariate techniques including principal component analysis and orthogonal partial least squares to latent structures discriminant analysis, were applied on all exons (n=614) of the TGFβ pathway. The scores plot based on splice index of individual exons, showed separate clusters of patients with dilated and patients with non-dilated aorta, thereby illustrating the potential importance of alternative splicing in TAA. In total, differential splicing was detected in 187 exons. Furthermore, the pattern of alternative splicing is clearly different between TAV and BAV patients. Differential splicing was specific for BAV and TAV patients in 40 and 86 exons, respectively, and splicing of 61 exons were shared between the two phenotypes. The occurrence of differential splicing was demonstrated in selected genes by RT-PCR. In summary, alternative splicing is a common feature of TAA formation. Our results suggest that dilatation in TAV and BAV patients has different alternative splicing fingerprints in the TGFβ pathway. |
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Authors:
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Sanela Kurtovic; Valentina Paloschi; Lasse Folkersen; Johan Gottfries; Anders Franco-Cereceda; Per Eriksson |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-24 |
Journal Detail:
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Title: Molecular medicine (Cambridge, Mass.) Volume: - ISSN: 1528-3658 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9501023 Medline TA: Mol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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