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Estrogen dependent CD4+ T cell specific transcriptomic pathways identified in premenopausal protection against hypertension

ABSTRACT: Estrogen dependent CD4+ T cell specific transcriptomic pathways identified in premenopausal protection against hypertension

PROVIDER: PRJNA667068 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12765162_1.fastq.gz	Fastqsanger.gz
	SRR12765162_2.fastq.gz	Fastqsanger.gz
	SRR12765163_1.fastq.gz	Fastqsanger.gz
	SRR12765163_2.fastq.gz	Fastqsanger.gz
	SRR12765164_1.fastq.gz	Fastqsanger.gz

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Estrogen dependent CD4+ T cell specific transcriptomic pathways identified in premenopausal protection against hypertension

Project description:Background: Premenopausal females are protected against T cell-dependent immune activation and development of angiotensin II (Ang II) hypertension compared to males and postmenopausal females. Therefore, the current study hypothesized that specific CD4+ T cell pathways are regulated by estrogen signlaing and Ang II, and contribute to sex differences in T cell cytokine secretion and renal inflammation. Methods and Results: Transcriptomic profiles of CD4+ T cells isolated from spleens of untreated (Control) and Ang II infused (Ang II) premenopausal C57BL/6 mice were examined via RNA sequencing. Ang II significantly regulated expression of 34 genes, of which 11 (Upregulated: CD163, PRG2, S100A9, MPO, CTSG, NGP, LCN2, S100A8; Downregulated: MARCO, IL1b, HSPA1B) were confirmed by real-time PCR. To determine the effect of estrogen on premenopausal expression of RNAseq identifed genes during Ang II infusion we used two models of estrogen signlaing disruption. Both animal wide knockdown of estrogen receptor a and 4-vinylcyclohexene diepoxide (VCD) induction of menopause, significantly altered expression of RNAseq identified genes. To examine the effect of T cell activation on RNAseq gene expression, CD4+ T cells from control and Ang II treated premenopausal and male mice were stimulated in vitro. Sex differences in T cell RNAseq gene expression were associated with sex differences in supernatant concentration of IL10, IL4, and IFNg and renal IL10, IL4, and IL2 content. Conclusions: These estrogen dependent T cell transcriptomic pathways and sex dependent functional differences in T cell cytokine secretion identify novel pathways that may mediate sex specific inflammatory responses during hypertension development.

2020-10-03 | GSE158946 | GEO

CD4+ T cell specific proteomic pathways identified in progression of hypertension across postmenopausal transition

Project description:Menopause is associated with an increase in the prevalence and severity of hypertension in women. Although premenopausal females are protected against T cell-dependent immune activation and development of angiotensin II (Ang II) hypertension, this protection is lost in postmenopausal females. Therefore, the current study hypothesized that specific CD4+ T cell pathways are regulated by sex hormones and Ang II to mediate progression from premenopausal protection to postmenopausal hypertension. Menopause was induced in C57BL/6 mice via repeated 4-vinylcyclohexene diepoxide (VCD) injections, while premenopausal females received sesame oil vehicle. A subset of premenopausal mice and all menopausal mice were infused with Ang II for 14 days (Control, Ang II, Meno/Ang II). Proteomic and phosphoproteomic profiles of CD4+ T cells isolated from spleens were examined.Ang II markedly increased CD4+ T cell protein abundance and phosphorylation associated with DNA and histone methylation in both premenopausal and postmenopausal females. Compared to premenopausal T cells, Ang II infusion in menopausal mice increased T cell phosphorylation of MP2K2, an upstream regulator of ERK, and was associated with upregulated phosphorylation at ERK targeted sites. Additionally, Ang II infusion in menopausal mice decreased T cell phosphorylation of TLN1, a key regulator of IL-2R and FOXP3 expression. These findings identify novel, distinct intracellular T cell pathways that influence T cell-mediated inflammation during postmenopausal hypertension.

2021-09-09 | PXD021233 | Pride

Genomic signature of parity in the breast of premenopausal women

Project description:Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer, in this study, we evaluated gene expression changes induced by parity in the breast of premenopausal women. Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers were performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted analysis of gene expression differences in P vs. NP women as a function of time since last FTP.

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Pembrolizumab, exemestane, and leuprolide in premenopausal estrogen receptor-positive/HER2-negative advanced breast cancer

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Pembrolizumab, exemestane, and leuprolide in premenopausal estrogen receptor-positive/HER2-negative advanced breast cancer

Project description:We evaluated the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with ER+/HER2− premenopausal MBC who had failed one to two lines of hormone therapy without chemotherapy.

2024-10-28 | GSE261380 | GEO

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Project description:The aim of the experiment was to identify the change of gene expression in human ovaries between premenopausal women and postmenopausal women based on DNA microarrays analysis. 8 human ovary samples were assembled from premenopausal women (n=4) and from postmenopausal women (n=4), respectively. The active transcription profiles of human ovaries were identified through DNA microarrays. Differentially expressed genes (DEGs) were identified as at least two-fold change with statistical significance. Enrichment of functions and signaling pathways analysis were performed based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes database.

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Molecular changes in premenopausal estrogen receptor-positive primary breast cancer after oophorectomy

Project description:For premenopausal women with primary ER+ breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore characterized the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER+ breast cancer for two weeks prior to mastectomy. Plasma estradiol concentrations decreased from 421±305 to 24.1±24.5 pmol/l (mean±sd) 24 hours after OvX and to 8.8±7.3pmol/l two weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR<1%) with an absolute mean fold-change (FC) ≥1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes, proliferation-associated genes and putative progesterone-regulated genes were strongly down-regulated. The gene expression changes did not differ according to HER2 status and correlated strongly with those after aromatase inhibitor (AI) treatment in 81 postmenopausal women. However, after OvX the mean FC was significantly higher compared to AI. In conclusion, changes in tumoural gene expression after OvX were largely similar but of a greater magnitude to those observed after AI in postmenopausal patients but OvX appeared to have a greater effect on progesterone-regulated genes than AI.

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