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Status: Bibliographieeintrag

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Verfasst von:Bhushan, Raghu [VerfasserIn]   i
 Zaradzki, Marcin [VerfasserIn]   i
 Kallenbach, Klaus [VerfasserIn]   i
Titel:An integrative systems approach identifies novel candidates in Marfan syndrome-related pathophysiology
Verf.angabe:Raghu Bhushan, Lukas Altinbas, Marten Jäger, Marcin Zaradzki, Daniel Lehmann, Bernd Timmermann, Nicholas P. Clayton, Yunxiang Zhu, Klaus Kallenbach, Georgios Kararigas, Peter N. Robinson
E-Jahr:2019
Jahr:24 January 2019
Umfang:10 S.
Fussnoten:Gesehen am 29.01.2020
Titel Quelle:Enthalten in: Journal of cellular and molecular medicine
Ort Quelle:Hoboken, NJ : Wiley-Blackwell, 2000
Jahr Quelle:2019
Band/Heft Quelle:23(2019), 4, Seite 2526-2535
ISSN Quelle:1582-4934
Abstract:Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in the FBN1 gene. Although many peripheral tissues are affected, aortic complications, such as dilation, dissection and rupture, are the leading causes of MFS-related mortality. Aberrant TGF-beta signalling plays a major role in the pathophysiology of MFS. However, the contributing mechanisms are still poorly understood. Here, we aimed at identifying novel aorta-specific pathways involved in the pathophysiology of MFS. For this purpose, we employed the Fbn1 under-expressing mgR/mgR mouse model of MFS. We performed RNA-sequencing of aortic tissues of 9-week-old mgR/mgR mice compared with wild-type (WT) mice. With a false discovery rate <5%, our analysis revealed 248 genes to be differentially regulated including 20 genes previously unrelated with MFS-related pathology. Among these, we identified Igfbp2, Ccl8, Spp1, Mylk2, Mfap4, Dsp and H19. We confirmed the expression of regulated genes by quantitative real-time PCR. Pathway classification revealed transcript signatures involved in chemokine signalling, cardiac muscle contraction, dilated and hypertrophic cardiomyopathy. Furthermore, our immunoblot analysis of aortic tissues revealed altered regulation of pSmad2 signalling, Perk1/2, Igfbp2, Mfap4, Ccl8 and Mylk2 protein levels in mgR/mgR vs WT mice. Together, our integrative systems approach identified several novel factors associated with MFS-aortic-specific pathophysiology that might offer potential novel therapeutic targets for MFS.
DOI:doi:10.1111/jcmm.14137
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1111/jcmm.14137
 Verlag: https://onlinelibrary.wiley.com/doi/abs/10.1111/jcmm.14137
 DOI: https://doi.org/10.1111/jcmm.14137
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Chemokine signalling
 Igfbp2 signalling
 Marfan syndrome
 Mfap4
 mgR/mgR
 RNA-sequencing
 Spp1
 TGF-beta signalling
 Transcriptomics
K10plus-PPN:1688780351
Verknüpfungen:→ Zeitschrift

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