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IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in mice [RNA-seq]

ABSTRACT: IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in mice [RNA-seq]

PROVIDER: PRJNA990942 | ENA |

REPOSITORIES: ENA

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IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating Egr1 in mice

Project description:IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating Egr1 in mice

| PRJNA990937 | ENA

IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating Egr1 in mice [ChIP-Seq]

Project description:IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating Egr1 in mice [ChIP-Seq]

| PRJNA990943 | ENA

IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating Egr1 in mice [ChIP-Seq]

Project description:Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides the evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.

2023-07-04 | GSE236455 | GEO

IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in mice [RNA-seq]

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IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating Egr1 in mice

Project description:This SuperSeries is composed of the SubSeries listed below.

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Egr1 regulates regenerative senescence and cardiac repair

Project description:Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA-sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and Agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, Agrin-induced senescence and repair require Egr1, activated by the integrin/FAK-ERK/Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype (SASP) components that promote ECM degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process.

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Egr1 is a master regulator of regenerative senescence and cardiac repair

Project description:The protein signatures in two mouse models of cardiac regeneration reveal enriched senescence gene sets, and Egr1 is the key regulator for regenerative senescence.Cathepsin S, a regenerative senescence-secreted component, promotes the degradation of the extracellular matrix, contributing to cardiac repair.

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Transient upregulation of EGR1 signaling enhances kidney repair by activating SOX9+ renal tubular cells

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