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A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

ABSTRACT: A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

PROVIDER: PRJNA661664 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12597900_1.fastq.gz	Fastqsanger.gz
	SRR12597900_2.fastq.gz	Fastqsanger.gz
	SRR12597901_1.fastq.gz	Fastqsanger.gz
	SRR12597901_2.fastq.gz	Fastqsanger.gz
	SRR12597902_1.fastq.gz	Fastqsanger.gz

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A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

Project description:A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

2020-09-06 | GSE157542 | GEO

A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction.

Project description:Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion of Tsc22d3-expressing macrophages-all of which may limit inflammatory damage. SRC stimulation with MCB-613 (and derivatives) is a potential therapeutic approach for inhibiting cardiac dysfunction after MI.

| S-EPMC7733826 | biostudies-literature

Steroid receptor coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress

Project description:We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction (MI). These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear. These studies were designed to identify the molecular and cellular circuitry that governs the anti-fibrotic effects of an MCB-613 derivative, MCB-613-10-1, in CFs. To achieve this, we performed cytokine profiling and whole transcriptome analyses of CF-derived signals in response to MCB-613-10-1. We identified the NRF2 pathway as an MCB-613-10-1 therapeutic target for promoting resistance to oxidative stress in CFs. We show that MCB-613-10-1 promotes cell survival of anti-fibrotic CFs exposed to oxidative stress by suppressing apoptosis. We demonstrate that an increase in HMOX1 expression contributes to CF resistance to oxidative stress-mediated apoptosis via a mechanism involving SRC co-activation of NRF2, hence reducing inflammation and fibrosis. We provide evidence that MCB-613-10-1 acts as a protectant against oxidative stress-induced mitochondrial damage. Our data reveal that SRC stimulation of the NRF2 transcriptional network promotes resistance to oxidative stress and highlights a mechanistic approach towards addressing pathologic cardiac remodeling.

2024-10-29 | GSE246877 | GEO

Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

Project description:RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of steroid receptor coactivator-2/nuclear receptor coactivator 2 (SRC-2/NCOA2)

2018-10-23 | GSE121584 | GEO

Genome-wide Profiling of Steroid Receptor Coactivator 2 in mouse liver

Project description:Steroid Receptor 2 (SRC-2) is a coactivator involved in hepatic metabolism. To better understand its temporal involvement in metabolism genome wide profiling was performed at 2 time ZT4 and ZT18 as well as in the SRC-2 knockout mouse.

2014-11-10 | GSE53039 | GEO

Oscheius sp. MCB isolate:MCB

Project description:Oscheius sp. MCB isolate:MCB Genome sequencing and assembly

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Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

Project description:Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

| PRJNA497833 | ENA

Tissue- and Pathway-Specific Metabolomic Profiles of the Steroid Receptor Coactivator (SRC) family

Project description:The rapidly growing family of coregulators of nuclear receptors includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have begun to emerge as important regulators of metabolic homeostasis, including the p160 Steroid Receptor Coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis in liver and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of SRC family members, we have performed targeted metabolomics analysis of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockout of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 knockout mice and their wild-type littermates in the fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC coactivator. Overall, we observed entire groups or subgroups of metabolites belonging to discrete metabolic pathways that were influenced in different tissues and/or feeding states due to ablation of individual SRC isoforms. Surprisingly, we identified very few metabolites that changed universally across the three SRC knockout models. These findings demonstrate that coactivator function has very limited redundancy even within the homologous SRC coactivator family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.

2013-04-10 | MTBLS30 | MetaboLights

Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enalbles Murine Embryo Implantation

Project description:Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enalbles Murine Embryo Implantation

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Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enalbles Murine Embryo Implantation

Project description:Using conditional knockout technology, we demonstrate that steroid receptor coactivator-2 (SRC-2) is essential for development of the receptive uterus for embryo implantation. Through bulk RNA-seq analysis, we reveal that endometrial SRC-2 is required for not only the induction of the expression of established genes associated with uterine receptivity but also for the expression of genes involved in endometrial epithelial changes that enable attachment and invasion of the embryo into the underlying stroma. Together, these RNA-seq results underscore the importance of SRC-2 as a transcriptional coregulator in the endometrium during the periimplantation period.

2023-11-20 | GSE237740 | GEO

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