Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of rapamycin on gene expresssion in mouse model of aortic dissection

ABSTRACT: Aortic dissection (AD) is a medical emergency that leads to sudden death. Effective medical therapy is not available because molecular mechanism of AD is poorly understood. We performed the transcriptome analysis in mouse AD model that was created by infusion of beta-aminopropionitrile, a collagen crosslink inhibitor, and angiotensin II. Bayesian network analysis of the transcriptome revealed several distinct gene clusters that were tightly co-regulated during AD development. Functional annotation analysis revealed that each gene cluster has distinct function, namely, cell proliferation, inflammation, cell locomotion and adhesion, and muscle differentiation. Among the gene clusters, cell proliferation cluster was the first to be activated during AD development. Cell proliferation before AD development was confirmed by immunoblotting of G1 cyclins. Immunostaining for Ki67 and cell markers revealed the proliferation of smooth muscle cells, fibroblasts, and monocytes in aortic tissue before AD development. Treatment of mice with rapamycin, an mTOR inhibitor, suppressed cell proliferative response in AD model. Rapamycin completely prevented AD when given before AD development, and effectively suppressed progression when given after AD development. Interestingly, transcriptome analysis showed that rapamycin strongly suppressed cell proliferation and muscle differentiation clusters, but its effect on inflammation cluster was modest. We concluded that mTOR constitutes an essential part of the molecular pathogenesis of AD by regulating cell proliferation, and represents a new therapeutic target.

ORGANISM(S): Mus musculus

PROVIDER: GSE138558 | GEO | 2020/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal mesenchymal cells represent a very small amount of cells. They are tightly bound to the bile duct and portal vascular structures, relying on basement membranes. In the present study, we set up a specific procedure to isolate portal mesenchymal cells, for scRNAseq analysis. We identified 16 distinct cell clusters, including fibroblasts (5 clusters), vascular smooth muscle cells (VSCMs, 5 clusters), endothelial cells (4 clusters), HSCs (1 cluster) and mesothelial cells (1 cluster).

2021-03-31 | GSE163777 | GEO

CD36 deficiency inhibits proliferation by cell cycle control in skeletal muscle cells

Project description:Obesity-related muscular dysfunction and relative muscle atrophy affect an increasing number of people. Elucidating the molecular mechanisms of skeletal muscle cell development and growth may contribute to the maintenance of skeletal muscle mass in obesity. Fatty acid translocase (FAT/CD36), as a long-chain fatty acid transport protein, is crucial for lipid metabolism and signaling. CD36 is known to function in myogenic differentiation, and whether it affects the proliferation of skeletal muscle cells and the underlying mechanisms remain unclear. In this study, the effect of CD36 deficiency on skeletal muscle cell viability and proliferation was examined using C2C12 myoblasts. Results showed that the deletion of CD36 enhanced the inhibitory effect of PA on the proliferation and the promotion of apoptosis in skeletal muscle cells. Intriguingly, the silencing of CD36 suppressed cell proliferation by preventing the cell cycle from the G0/G1 phase to the S phase in a cyclin D1/CDK4-dependent manner. Overall, we demonstrated that CD36 was involved in skeletal muscle cell proliferation by cell cycle control, and these findings might facilitate the treatment of obesity-related muscle wasting.

2022-05-27 | GSE204686 | GEO

Regulatory function of Pja2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells

Project description:Praja2 (Pja2), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved not only in several types of cancer but also in neurological diseases and disorders. However, the underlying genetic mechanism of Pja2 regulation in the nervous system remains unclear. To study the cellular and molecular function of Pja2 in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of Pja2 in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. We found that the expression of AD markers including App, Mapt and Gsap could be inhibited by Pja2 overexpression and activated by Pja2 knockdown. In addition, HT-22 cell proliferation was enhanced by Pja2 upregulation and suppressed by its downregulation. We also applied RNA-Seq to evaluate and quantify the targets that responded to the enforced expression of Pja2. In particular, P2rx3 and P2rx7, which have different expression patterns in the critical calcium signaling pathway, were shown to mediate the regulatory effect of Pja2 in HT-22 cells. Functional studies indicated that Pja2 regulated HT-22 cell development and AD marker genes by inhibiting P2rx3 but promoting P2rx7, a gene downstream of P2rx3. In conclusion, our results provide new insights into the regulatory function of the gene Pja2 in MHNCs, underscoring the potential relevance of this molecule to the pathophysiology of AD.

2020-12-15 | E-MTAB-6464 | biostudies-arrayexpress

Gene expression data from rapamycin resistant and sensitive cell lines

Project description:The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation. Inhibitors of mTOR are being evaluated as anti-tumor agents. Given the emerging role of microRNAs (miRNAs) in tumorgenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Rapamycin resistant myogenic cells developed by long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumor-suppressor miRNAs. Antagonists of oncogenic miRNA families and mimics of tumor suppressor miRNAs (let-7) restored rapamycin sensitivity in resistant tumor cells. This study identified miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors. Total RNA extraction and hybridization on Affymetrix microarrays of rapamycin sensitive (RS) cells (BC3H1, mouse brain tumor cell line with myogenic properties, ATCC) cultured in Dulbecco’s modified essential medium (DMEM) media supplemented with 20% fetal bovine serum (FBS), penicillin (100 U/ml) and streptomycin (100 mg/ml). Rapamycin resistant cells (RR1) were developed by culturing BC3H1 cells in the presence of 1 uM rapamycin for 6 months. Three samples in triplicates: 1) Rapamycin sensitive cells treated with DMSO for 24 h(BC3H1, reference), 2) Rapamycin sensitive cells treated for 24 h with 100 nM rapamycin (BC3H1+R), 3) Rapamycin resistant cells constantly treated with 1uM Rapamycion (RR1+R).

2013-02-08 | E-GEOD-19885 | biostudies-arrayexpress

Differentially regulated genes in TOR knockdown Arabidopsis lines

2012-12-18 | GSE42968 | GEO

MicroRNAs mediate rapamycin resistance in a myogenic tumor cell line

2013-02-08 | GSE19916 | GEO

Gene expression data from rapamycin resistant and sensitive cell lines

2013-02-08 | GSE19885 | GEO

Differentially regulated genes in TOR knockdown Arabidopsis lines

Project description:Rapamycin-sensitive transgenic Arabidopsis lines (BP12) expressing yeast FK506 Binding Protein12 (FKBP12) were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf and shoot growth and development leading to poor nutrient uptake and light energy utilization. Genetic and physiological studies together with RNA-Seq and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and lifespan in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, ribosomal RNA and protein synthesis. Arabidopsis WT (Col)and BP12-2 (TOR knockdown line) seedlings at 15 DAG were treated with rapamycin for 3 days by transferring from 0.5 MS medium to 0.5 MS+10 ug/ml rapamycin. Triplicate samples of rapamycin treated WT and BP12-2 seedlings were used for RNA-Seq analysis (Illumina Hiseq 2000). Paired-end alignments were obtained through aligning short reads onto the reference Arabidopsis Genome (TAIR9) using Bowtie. More than 80% of the reads mapped onto the genome. Htseq-count was used to count the reads from the Bowtie derived output files. Differential expressed genes were identified using edgeR. The FDR-corrected P value for differential expression was set to be <=0.05.

2012-12-18 | E-GEOD-42968 | biostudies-arrayexpress

Interaction between mitoNEET and NAF-1 in cancer cells

Project description:The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. MitoNEET and NAF-1 are also implicated in a number of other human pathologies including diabetes, neurodegeneration and heart disease, as well as in development, differentiation and aging. Previous studies suggested that mNT and NAF-1 could function in the same pathway in cancer cells, preventing the over-accumulation of iron and reactive oxygen species (ROS) in mitochondria. Nevertheless, it is unknown whether these two proteins interact in cells, and how they mediate their function. Here we demonstrate, using yeast two-hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling analysis (DCA), RNA- sequencing, ROS and iron imaging, and single and double shRNA lines with suppressed mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1 interact in cancer cells and function in the same cellular pathway. We further show using an in vitro cluster transfer assay that mNT can transfer its clusters to NAF-1. Our study suggests that mNT and NAF-1 could function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the levels of iron and Fe-S clusters under control in the mitochondria of cancer cells, thereby preventing the activation of apoptosis and/or autophagy and thus promoting rapid cellular proliferation.

2017-03-25 | GSE87626 | GEO

Transcriptomic profiling of sporadic Alzheimer’s disease patients

Project description:Alzheimer’s disease (AD) manifested before age 65 is commonly referred to as early-onset AD (EOAD). While the majority (> 90%) of EOAD cases are not caused by autosomal-dominant mutations in PSEN1, PSEN2, and APP, they do have a higher heritability (92–100%) than sporadic late-onset AD (LOAD, 70%). Although the endpoint clinicopathological changes, i.e., Aβ plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous. This heterogeneity, leading to temporally distinct age at onset (AAO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes. Further, analyses of large postmortem brain cohorts demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling. Areas of the brain less affected by AD pathology at early disease stages—such as the primary visual cortex—exhibit similar transcriptomic dysregulation as those regions traditionally affected and, therefore, may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology. To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD) using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AAO may not directly correlate with the identity and severity of AD endotypes.

2022-10-12 | GSE203206 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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