Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

ABSTRACT: Background: Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. Results: We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. Conclusions: Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 x 10-6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater. Keywords: disease state comparison; Marfan syndrome; cultured skin fibroblasts

ORGANISM(S): Homo sapiens

PROVIDER: GSE8759 | GEO | 2007/09/14

SECONDARY ACCESSION(S): PRJNA102035

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Ang II type 1a receptor in Marfan syndrome

Project description:Using Cdh5-Cre and Sm22-Cre transgenes to characterize the impact of disruption of the angiotensin II type 1a receptor (AT1ar) in vascular endothelial and smooth muscle cells, respectively, of wild type (WT) mice compared to fibrillin-1 hypomorphic mice (Fbn1mgR/mgR mice) that replicate early onset progressively severe Marfan syndrome (MFS) with dissecting thoracic aortic aneurysm (TAA).

2018-01-30 | GSE109797 | GEO

Murine Marfan Syndrome Sildenafil Treatment

Project description:Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene. While aortic rupture is the major cause of mortality in MFS, patients also suffer from poorly understood pulmonary complications. Loss of basal nitric oxide (NO) production and vascular integrity are proposed to take part in MFS aortic root disease, yet their contribution to lung complications has yet to be determined. Due to its capacity to potentiate the vasodilatory NO/cyclic guanylate monophosphate signaling pathway, we assessed whether the phosphodiesterase-5 (PDE5) inhibitor sildenafil (SIL) could attenuate aortic root remodelling and emphysema in a mouse model of MFS. Despite increasing NO-dependent vasodilation, SIL unexpectedly elevated mean arterial blood pressure, failed to inhibit MFS aortic root dilation and exacerbated elastic fibrefiber fragmentation. In the lung, early pulmonary artery dilation observed in untreated MFS mice was delayed by SIL treatment, and severe emphysema-like alveolar destruction was prevented. In addition, improvements in select parameters of lung function were documented. Subsequent micro-array analyses showed changes to gene signatures involved in the inflammatory response in MFS lung treated with SIL, without significant downregulation of connective tissue or TGF-β signalling genes. Since PDE5 inhibition leads to improved lung histopathology and function, the effects of SIL against emphysema warrant further investigation in the settings of MFS despite limited efficacy on aortic root remodelling.

2019-03-19 | GSE128481 | GEO

Understanding the role of TGFbeta signaling on aortic aneurysm and rupture using Marfan syndrome mouse models

Project description:Although abnormal TGFbeta signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, the precise role of TGFbeta signaling in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to investigate the role of TGFbeta signaling in molecular pathways of pathogenesis associated with development of aortic aneurysm and aortic rupture. This study reports an isoform-specific effect of TGFbeta in MFS aortic disease and the effects of deleting the first hybrid domain of fibrillin-1 on TGFbeta signaling. Distinct molecular differences in mouse models of aneurysm (Fbn_GT-8_plus), of aneurysm and rupture (Fbn1_GT-8_H1delta), and of microdissection (Fbn1_H1delta_plus) were identified, which associated with TGFbeta signaling and extracellular matrix composition, possibly contributing to the development of dissection and rupture. These findings offer new insights into the pathophysiological mechanisms that potentially drive initiation of aortic dissection and could pave the way for development of new treatment targets of aortic disease.

2023-10-09 | PXD036222 | Pride

microRNA microarray of aortae from 10-week male Fbn1mgR/mgR and wild-type mice [10-week_miRNA]

Project description:Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1mgR/mgR) revealed a spectrum of differentially regulated miRNAs. Bioinformatic analyses predicted the involvement of these miRNAs in inflammatory and extracellular matrix related pathways. Complementing mRNA microarray demonstrated the upregulation of multiple pro-inflammatory cytokines and matrix metalloproteases. Correlation analyses between the altered miRNAs and mRNAs present miR-122, the most downregulated miRNAs in the TAA tissue of Fbn1mgR/mgR, to be a core regulatory miRNA to pro-inflammatory cytokines, Ccl2 and Il1b, which were upregulated in the TAA tissues. At 10 weeks, the number of differentially regulated miRNAs (>2-fold) increased to 129 with 5 down- and 124 upregulated miRNAs

2022-05-21 | GSE199283 | GEO

microRNA microarray of aortae from 4-week male Fbn1mgR/mgR and wild-type mice [4-week_miRNA]

Project description:Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1mgR/mgR) revealed a spectrum of differentially regulated miRNAs. Bioinformatic analyses predicted the involvement of these miRNAs in inflammatory and extracellular matrix related pathways. Complementing mRNA microarray demonstrated the upregulation of multiple pro-inflammatory cytokines and matrix metalloproteases. Correlation analyses between the altered miRNAs and mRNAs present miR-122, the most downregulated miRNAs in the TAA tissue of Fbn1mgR/mgR, to be a core regulatory miRNA to pro-inflammatory cytokines, Ccl2 and Il1b, which were upregulated in the TAA tissues. 3 miRNAs were downregulated and 14 upregulated more than 2-fold

2022-05-21 | GSE199282 | GEO

Dissecting aortic aneurysm in Marfan syndrome is associated with losartan-sensitive transcriptomic modulation of aortic cells

Project description:To improve our limited understanding of the pathogenesis of thoracic aortic aneurysm (TAA) leading to acute aortic dissection, we used single-cell RNA sequencing to profile disease-relevant transcriptomic changes of aortic cell populations in a well-characterized mouse model of the most commonly diagnosed form of Marfan syndrome (MFS). As result,MFSmod were identified only in the aorta of Fbn1mgR/mgR mice. In situ hybridizations of diagnostic transcripts located MFSmod cells to the intima of Fbn1mgR/mgR aortas. Consistent with angiotensin II type I receptor (At1r) contribution to TAA development, MFSmod cells were absent in the aorta of Fbn1mgR/mgR mice treated with the At1r antagonist losartan. Altogether, our findings indicate that a discrete dynamic alteration of aortic cell identity is associated with dissecting TAA in MFS mice and increased risk of aortic dissection in MFS patients.

2023-06-27 | GSE227776 | GEO

mRNA microarray of aortae from 10-week male Fbn1mgR/mgR and wild-type mice [10-week_mRNA]

Project description:Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1mgR/mgR) revealed a spectrum of differentially regulated miRNAs. Bioinformatic analyses predicted the involvement of these miRNAs in inflammatory and extracellular matrix related pathways. Complementing mRNA microarray demonstrated the upregulation of multiple pro-inflammatory cytokines and matrix metalloproteases. Correlation analyses between the altered miRNAs and mRNAs present miR-122, the most downregulated miRNAs in the TAA tissue of Fbn1mgR/mgR, to be a core regulatory miRNA to pro-inflammatory cytokines, Ccl2 and Il1b, which were upregulated in the TAA tissues. A total of 471 mRNAs were up-regulated (green) and 253 downregulated (red) more than 2-fold (p<0.05) in the aneurysmal versus the wild-type tissues.

2022-05-21 | GSE199284 | GEO

17 -estradiol impedes aortic root dilation and rupture in male Marfan mice

Project description:Thoracic aortic aneurysms have a higher prevalence in male patients compared to female patients. Marfan syndrome causes a hereditary form of TAA with dilation of the aortic root. Male patients with Marfan syndrome are more likely than women to have aortic dilation and dissection and mouse models of Marfan syndrome demonstrate larger aortic roots in males compared to females even after adjustment for body size. Similar sex disparities are present in patients and models of abdominal aortic aneurysms where estrogen has been demonstrated to attenuate aneurysm formation perhaps through anti-inflammatory mechanisms. In this study we demonstrate the effects of estrogen on aortic dilation and rupture in a Marfan mouse model and we investigate if these effects operate through suppression of complement components of the immune system.

2024-02-14 | PXD037853 | Pride

Subcellular pathways shared by afflicted patients and mutant mice identify a new drug treatment for aortic aneurysm in Marfan syndrome

Project description:We analyzed differentially expressed genes in smooth muscle cells derived from the thoracic aorta of Marfan Syndrome (MFS) patients and control subjects to identify cell biological mechanisms contributing to thoracic aoritc aneurysm (TAA) development and rupture. These mechanisms were used to identify a potential drug treatment to mitigate TAA progression. We analyzed differentially expressed genes in whole aorta of P16 MFS mice vs WT mice to identify cell biological mechanisms contributing to thoracic aoritc aneurysm (TAA) development and rupture. These mechanisms were used to identify baclofen as a potential drug treatment to mitigate TAA progression. The effect of baclofen on gene expression in WT and MFS was documented in P60 mice that received treatment since P16.

2019-11-18 | GSE128101 | GEO

Inhibition of the multifunctional homeodomain-interacting protein kinase 2 (HIPK2) alleviates thoracic aortic disease in mice with progressively severe Marfan syndrome

Project description:Thoracic aortic aneurysm (TAAs) are a severe complication in Marfan Symdrome (MFS), often leading to dissection and premature death. To identify potential drug targets for the treatment for TAAs we used gene expression profiles from MFS mice and patients to predict kinases that regulate gene expression. Among the top predictions was the kinase HIPK2. Ubiquitous post-natal inactivation of the HIPK2 gene, as well as chronic administration of an allosteric inhibitor of HIPK2/Smad3 interaction, increased the survival of MFS mice and improved multiple surrogate parameters.

2021-10-27 | GSE145903 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data