Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TRIM21 aggravates cardiac injury after myocardial infarction via promoting M1 macrophage polarization

ABSTRACT: Macrophage polarization followed by acute myocardial infarction (MI) is essential for the regulation of inflammation and scar formation. Tripartite motif-containing protein 21 (TRIM21), a member of E3 ubiquitin ligases, is a crucial mediator in the process of inflammation and heart failure. However, the potential roles of TRIM21 in modulating post-MI inflammation and macrophage polarization remain elusive. We detected that the levels of TRIM21 were significantly reduced in macrophages of WT mice after MI. In contrast, MI was ameliorated in TRIM21 knockout (TRIM21-/-) mice with improved cardiac remodeling, characterized by a marked decrease in mortality, increased wall thickness, and improved cardiac function in comparison with wild-type (WT) MI mice. Importantly, TRIM21 deficiency decreased the post-MI apoptosis and DNA damage in the hearts of mice, and the accumulation of M1 phenotype macrophages in infarcted hearts significantly decreased in TRIM21-/- mice compared with WT controls. Mechanistically, depletion of TRIM21 orchestrated the process of M1 macrophage polarization via a PI3K/Akt signaling pathway. Overall, these data reveal that TRIM21 drives the inflammatory response and cardiac remodeling after MI via stimulating M1 macrophage polarization through a PI3K/Akt signaling pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE214696 | GEO | 2022/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction

Project description:Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial pro-inflammatory response followed by an anti-inflammatory or reparative response post-MI is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and essential for cardiac repair as they can adopt both pro-inflammatory (M1) or anti-inflammatory/reparative (M2) phenotypes to modulate inflammatory and reparative response, respectively. YAP and TAZ are the key mediators of the Hippo signaling pathway and essential for cardiac regeneration and repair. However, their role in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing M1 or M2 polarization. Genetic deletion of YAP/TAZ leads to impaired M1 polarization and enhanced M2 polarization. Consistently, YAP activation/overexpression enhanced M1 and impaired M2 polarization. We show that YAP/TAZ promote M1 polarization by increasing IL6 expression, and impede M2 polarization by decreasing Arg1 expression through interaction with the HDAC3-NCoR1 repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, and hypertrophy and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro- and anti-inflammatory responses post-MI.

2020-10-02 | GSE158889 | GEO

Comparison of gene expression in cardiac macrophages from P1 or P14 mice 3 days following MI

Project description:Myocardial infarction (MI) leads to cardiomyocyte death, which triggers an immune response that clears debris and restores tissue integrity. In the adult heart, the immune system facilitates scar formation, which repairs the damaged myocardium but compromises cardiac function. In neonatal mice, the heart can regenerate fully without scarring following MI; however, this regenerative capacity is lost by P7. The signals that govern neonatal heart regeneration are unknown. By comparing the immune response to MI in mice at P1 and P14, we identified differences in the magnitude and kinetics of monocyte and macrophage responses to injury. Using a cell-depletion model, we determined that heart regeneration and neoangiogenesis following MI depends on neonatal macrophages. Neonates depleted of macrophages were unable to regenerate myocardia and formed fibrotic scars, resulting in reduced cardiac function and angiogenesis. Immunophenotyping and gene expression profiling of cardiac macrophages from regenerating and nonregenerating hearts indicated that regenerative macrophages have a unique polarization phenotype and secrete numerous soluble factors that may facilitate the formation of new myocardium. Our findings suggest that macrophages provide necessary signals to drive angiogenesis and regeneration of the neonatal mouse heart. Modulating inflammation may provide a key therapeutic strategy to support heart regeneration. Total RNA was isolated from CD11b+Ly6G- cells sorted from hearts 3 days following ligation of LAD. 6 samples total: Triplicates of cells from P1 mice and from P14 mice

2014-01-31 | E-GEOD-54530 | biostudies-arrayexpress

Gene expression profile of cardiac macrophages at different timepoints after myocardial infarction

Project description:Myocardial infarction (MI) causes sterile inflammation, which is characterized by recruitment and activation of innate and adaptive immune system cells. We have delineated the temporal dynamics of immune cell accumulation following MI by flow cytometry. Macrophages were numerically the predominant cells infiltrating the infarcted myocardium, increasing in number over the first week post-MI. Macrophages are functionally heterogeneous, and can be classified into M1 and M2 macrophages, respectively, based on surface-marker expression. M1 macrophages dominated at 1-3 days post-MI, whereas M2 macrophages represented the predominant macrophage subset after 5 days. We used microarrays to examine the gene expression profiles of the macrophages sorted from the hearts at different timepoints after MI. We identified the kinetics of gene expression of cardiac macrophage after MI.

2017-03-27 | GSE88924 | GEO

TRIM21 aggravates cardiac injury after myocardial infarction via promoting M1 macrophage polarization

Project description:TRIM21 aggravates cardiac injury after myocardial infarction via promoting M1 macrophage polarization

| PRJNA886696 | ENA

Comparison of gene expression in cardiac macrophages from P1 or P14 mice 3 days following MI

2014-01-31 | GSE54530 | GEO

Transcript profiling of WT and SIRPα KO BMDMs post-M1 activation in the presence of mCD47.ex

Project description:To compare the inflammatory responses of WT and SIRPα KO macrophage, we performed a complete transcript profiling of WT and SIRPα-KO M1 macrophage using transcriptome sequencing as a discovery platform. SIRPα-KO mice and WT mice were kept under the same condition. BMDMs were produced from WT and SIRPα-KO mice followed by M1 polarization. RNA was then isolated from the same number of BMDMs.

2021-03-19 | GSE169177 | GEO

The pathological alterations in hearts from polycystic ovary syndrome mice [male_PAMH]

Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disease in reproductive-aged women, is associated with an increased prevalence and extent of coronary artery disease. However, the underlying mechanism remains unclear. Here, we observed that hearts from PCOS mice were characterized by increased total macrophage accumulation. Monocyte-derived macrophages were significantly increased in the hearts of PCOS mice owing to enhanced circulating monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Compared with non-PCOS animals, PCOS-induced mice showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional Vcam1 silencing in PCOS mice significantly suppressed cardiac inflammation and improved post-MI cardiac injury. Our data documented new mechanisms through which PCOS may affect cardiovascular health in women.

2024-01-02 | GSE238074 | GEO

The pathological alterations in hearts from polycystic ovary syndrome mice [NWZ_HFD]

2024-01-02 | GSE238073 | GEO

The pathological alterations in hearts from polycystic ovary syndrome mice [female_PAMH]

2024-01-02 | GSE238072 | GEO

Skatole attenuates osteoarthritis by protecting chondrocytes and mediating macrophage repolarization through regulating the NFκB/MAPK signaling pathway and metabolic reprogramming

Project description:Osteoarthritis (OA) is the most common joint disease, but there are currently no disease-modifying OA drugs (DMOADs) yet approved by the regulatory agencies. Regulating macrophage polarization can alleviate synovial inflammation and then repair articular cartilage damage, providing a new target for OA treatment. Here, we found that Skatole can modulate macrophage polarization and attenuate OA. Skatole hindered M1 macrophage polarization while promoting M2 macrophage polarization. Mechanistically, Skatole activated Stat6, suppressed the phosphorylation of IKK, IκBα, and p65 in NFκB signaling pathway, and inhibited MAPK signaling activation. RNA-seq analysis revealed that Skatole downregulated the expression of inflammation-related genes, while upregulating genes involved in glutathione metabolism and oxidative phosphorylation, thereby reducing ROS levels and inhibiting M1 macrophage polarization. Moreover, conditional medium (CM) from M1 macrophages treated with Skatole balanced anabolism and catabolism in mouse chondrocytes while inhibiting cell apoptosis. Intriguingly, in IL1β-treated chondrocytes, Skatole directly suppressed inflammation and catabolism, without significantly affecting cell apoptosis or anabolism; In vivo experiments showed that Skatole increased M2 polarization and decreased M1 polarization of synovial macrophages, alleviated synovitis, and lessend articular cartilage damage in destabilization of medial meniscus (DMM)-induced OA mice. Our finding suggest that Skatole has the potential to function as a DMOAD.

2025-02-12 | GSE261400 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data