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Estrogen-mediated downregulation of HIF-1 signaling in B lymphocytes influences postmenopausal bone loss

ABSTRACT: Estrogen-mediated downregulation of HIF-1 signaling in B lymphocytes influences postmenopausal bone loss

PROVIDER: PRJNA687752 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13289338_1.fastq.gz	Fastqsanger.gz
	SRR13289338_2.fastq.gz	Fastqsanger.gz
	SRR13289339_1.fastq.gz	Fastqsanger.gz
	SRR13289339_2.fastq.gz	Fastqsanger.gz
	SRR13289340_1.fastq.gz	Fastqsanger.gz

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Estrogen-mediated downregulation of HIF-1 signaling in B lymphocytes influences postmenopausal bone loss

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Project description:Natural control of HIV infection in Elite Controllers (EC) is a characteristic of <1% of HIV infected individuals. Extensive research has tried to elucidate the mechanism of control without any concrete results due to a large heterogeneity in the EC group, both between the sexes and how they obtain control. Therefore, we sought to identify signaling pathways associated with the EC phenotype by proteomics (all male) and transcriptomic (male and female) analysis. Further, we integrated the proteomics and transcriptomic analysis in the male cohort. We found that HIF signaling and downstream glycolysis are specific traits of the EC phenotype. Within this pathway ENO1 was upregulated in EC on a protein level irrespective of sex. We also performed targeted transcriptomic analysis where we identified HIF target genes as specifically de-regulation of in EC group. Namely, we observed an increase in the antiviral transcript GPS2, while CXCR4 and EIF5A were down regulated. Although we could not detect any difference in protein levels of HIF-1α in total PBMCs, we observed a higher portion of HIF-1α and HIF-1β in the nuclei of CD4+ and CD8+ T cells indicating an increased activation of HIF signaling in the male EC. Furthermore, the intracellular glucose levels were elevated in EC even as metabolite transporter expression of Glut1 and MCT-1 was decreased in lymphocytes showing that the EC have a unique metabolic uptake and secretion profile. Combined our data indicate the role HIF-1 signaling and glycolysis has in natural control of HIV infection.

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2019-06-02 | MTBLS136 | MetaboLights

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