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Homo sapiens

ABSTRACT: Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

PROVIDER: PRJNA251404 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1313290_1.fastq.gz	Fastqsanger.gz
	SRR1313290_2.fastq.gz	Fastqsanger.gz
	SRR1313300_1.fastq.gz	Fastqsanger.gz
	SRR1313300_2.fastq.gz	Fastqsanger.gz
	SRR1313291_1.fastq.gz	Fastqsanger.gz

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Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

2014-06-10 | GSE58150 | GEO

Integrative DNA, RNA and protein evidence connects TREML4 to coronary artery calcification

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Total RNA sequencing data of murine bone marrow derived macrophages from WT and Treml4 deficient mice

Project description:Treml4 has been recently characterized as a protein-coding gene of the Trem family. It has been shown that its expression is controlled by two cis- eQTL's and that the minor allele a these locuses confers up to 6.5 fold increased relative risk of human coronary arterial calcification (CAC). Since Treml4 expression is confined to the myeloid compartment, we aimed to, first, determined if Treml4 expression correlates to inflammatory activation and, second, investigate how inflammatory gene expression is affected by Treml4 expression status utlizing a global knockdown mouse for Treml4.

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Project description:Treml4 has been recently caracterized as a protein-coding gene of the Trem family. It has been shown that its expression is controlled by two cis- eQTL's and that the minor allele a these locuses confers up to 6.5 fold increased relative risk of human coronary arterial calcification (CAC). Since Treml4 expression is confined to the myeloid compartment, we aimed to, first, determined if Treml4 expression correlates with lipid laden macrophages and, second, investigate how gene expression is affected by Treml4 expression status utlizing a global knockdown mouse for Treml4 under the apolipoprotein deficient background.

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RNA-seq of human PBMC's and blood derived macrophages from healthy donors carrying the common (non permissive Treml4 expression) or minor (permissive Treml4 expression) allele for rs2803496 which controls Treml4 expression

Project description:Treml4 has been recently characterized as a protein-coding gene of the Trem family. It has been shown that its expression is controlled by two cis- eQTL's and that the minor allele a these locuses confers up to 6.5 fold increased relative risk of human coronary arterial calcification (CAC). Since Treml4 expression is confined to the myeloid compartment, we aimed to, first, determine if Treml4 expression correlates to inflammatory activation and, second, investigate how inflammatory gene expression is affected by Treml4 expression status in donors carrying the minor allele for a rs2803496.

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Project description:Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced polyubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation enhanced VC. HDAC1 protein, but not mRNA, was reduced in cell and animal calcification models and in human calcified coronary artery. In the calcification-provoking condition, proteasomal degradation of HDAC1 preceded VC. The calcification-provoking condition induced MDM2 E3 ligase, which then resulted in HDAC1 K74 polyubiquitination. Overexpression of MDM2 enhanced VC, whereas loss of MDM2 blunted it. Decoy peptides spanning HDAC1 K74 and RG 7112, an MDM2 inhibitor, prevented VC in vivo and in vitro. These results demonstrate a previously unknown ubiquitination pathway and suggest MDM2-mediated HDAC1 polyubiquitination as a new therapeutic target in VC. Calcification was induced in rat aorta vascular smooth muscle cells with inorganic phosphate (Pi). Total RNA were extracted from the cells 3 and 6 days later. mRNA profile of the sample was compared with normal control.

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