Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration

ABSTRACT: The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration, but many questions remain about its exact role. Here we show that MyD88, a key component of the innate immune response, controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. We find in cryoinjured myd88-/- ventricles a significant reduction in neutrophil and macrophage numbers as well as the expansion of a collagen-rich endocardial population. Further analyses reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium and increased myofibroblasts and scarring. Notably, endothelial-specific overexpression of myd88 reverses these neutrophil, fibrotic, and scarring phenotypes. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a target of the MyD88-signaling pathway, and using loss- and gain-of-function tools show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis during tissue regeneration.

ORGANISM(S): Danio rerio

PROVIDER: GSE262351 | GEO | 2024/07/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst169)

Project description:The innate immune system is triggered rapidly after injury and its spatiotemporal dynamics are critical for successful regeneration. MyD88 is a key component of the innate immune response; however, its role during regeneration remains unclear. Here we show that MyD88 controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. Our data reveal a significant reduction in pro-inflammatory neutrophil and macrophage populations, as well as the expansion of a collagen-rich endocardial population in cryoinjured myd88-/- ventricles. Consistent with these findings, we observed increased myofibroblasts, fibrin abundance, and scarring in myd88-/- ventricles. Transcriptomic analyses of endocardial cells and immunostaining experiments reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium. Moreover, loss of MyD88 impairs cardiomyocyte proliferation and protrusive activity towards the injured area. Notably, endothelial-specific overexpression of myd88 reverses the neutrophil, fibrotic, and scarring phenotypes in cryoinjured myd88-/- ventricles. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a transcriptional target of the MyD88-signaling axis and using loss- and gain-of-function tools show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis, thereby emphasizing the strong impact of the innate immune response during tissue regeneration.

2024-07-29 | GSE262247 | GEO

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration

Project description:This SuperSeries is composed of the SubSeries listed below. The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration, but many questions remain about its exact role. Here we show that MyD88, a key component of the innate immune response, controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. We find in cryoinjured myd88-/- ventricles a significant reduction in neutrophil and macrophage numbers as well as the expansion of a collagen-rich endocardial population. Further analyses reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium and increased myofibroblasts and scarring. Notably, endothelial-specific overexpression of myd88 reverses these neutrophil, fibrotic, and scarring phenotypes. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a target of the MyD88-signaling pathway, and using loss- and gain-of-function tools show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis during tissue regeneration.

2024-07-29 | GSE262248 | GEO

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst139)

Project description:The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration, but many questions remain about its exact role. Here we show that MyD88, a key component of the innate immune response, controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. We find in cryoinjured myd88-/- ventricles a significant reduction in neutrophil and macrophage numbers as well as the expansion of a collagen-rich endocardial population. Further analyses reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium and increased myofibroblasts and scarring. Notably, endothelial-specific overexpression of myd88 reverses these neutrophil, fibrotic, and scarring phenotypes. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a target of the MyD88-signaling pathway, and using loss- and gain-of-function tools show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis during tissue regeneration.

2024-07-29 | GSE262169 | GEO

Injury-activated endocardium plays structural and signalling roles in zebrafish heart regeneration

Project description:The zebrafish heart remarkably regenerates after a severe ventricular damage followed by inflammation, fibrotic tissue deposition and removal concomitant with cardiac muscle replacement. We have investigated the role of the endocardium in this regeneration process. 3D-whole mount imaging in injured hearts revealed that GFP-labelled endocardial cells in ET33mi-60A transgenic fish become rapidly activated and highly proliferative at 3 days post cryoinjury (dpci). Endocardial cells extensively expand within the injury site and organize to form a coherent structure at 9 dpci that persists throughout the regeneration process. Upon injury, endocardial cells strongly up-regulate the Notch pathway ligand delta like4 (dll4) and the Notch receptors notch1b, notch2 and notch3. Expression profiling showed that Notch signalling inhibition affects endocardial gene expression and genes related to extracellular matrix remodelling and inflammation. Gain- and loss-of-function experiments revealed that Notch is required for the organization of the endocardium, attenuation of the inflammatory response and cardiomyocyte proliferation. These results demonstrate a novel structural and signalling role for the endocardium during heart regeneration.

2017-03-31 | GSE68650 | GEO

flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response

Project description:VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years; however, many challenges remain. Here we investigate a different approach to augmenting VEGFA bioavailability, one that achieves more physiological VEGFA concentrations by deleting VEGFR1/FLT1, a VEGFA decoy receptor. We find that, following cryoinjury, zebrafish flt1 mutant hearts display enhanced coronary revascularization and endocardial expansion, increased cardiomyocyte dedifferentiation and proliferation, and decreased scarring. Suppressing Vegfa signaling in flt1 mutants abrogates the beneficial effects of flt1 deletion. Transcriptomic analyses of cryoinjured flt1 mutant hearts revealed enhanced endothelial MAPK/ERK signaling and downregulation of the transcription factor gene egr3. Using genetic tools, we observe egr3 upregulation in the regenerating endocardium and find that Egr3 promotes myofibroblast differentiation. These data suggest that with enhanced VEGFA bioavailability, the cardiac endothelium limits myofibroblast differentiation via egr3 downregulation, thereby providing a more permissive microenvironment for cardiomyocyte replenishment after injury.

2024-11-12 | GSE264406 | GEO

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration

Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration

| PRJNA1090894 | ENA

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration

Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration

| PRJNA1091566 | ENA

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst139)

Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst139)

| PRJNA1090509 | ENA

The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst169)

Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst169)

| PRJNA1090898 | ENA

Endocardial identity is established during early somitogenesis by Bmp signalling acting upstream of npas4l and etv2

Project description:The endocardium plays important roles in the development and function of the vertebrate heart; however, few molecular markers of this tissue have been identified and little is known about what regulates its differentiation. Here, we describe the Gt(SAGFF27C); Tg(4xUAS:egfp) line as a marker of endocardial development in zebrafish. Transcriptomic comparison between endocardium and pan-endothelium confirms molecular distinction between these populations and time-course analysis suggests differentiation as early as eight somites. To investigate what regulates endocardial identity, we employed npas4l, etv2 and scl loss-of-function models. Endocardial expression is lost in npas4l mutants, significantly reduced in etv2 mutants and only modestly affected upon scl loss-of-function. Bmp signalling was also examined: overactivation of Bmp signalling increased endocardial expression, whereas Bmp inhibition decreased expression. Finally, epistasis experiments showed that overactivation of Bmp signalling was incapable of restoring endocardial expression in etv2 mutants. By contrast, overexpression of either npas4l or etv2 was sufficient to rescue endocardial expression upon Bmp inhibition. Together, these results describe the differentiation of the endocardium, distinct from vasculature, and place npas4l and etv2 downstream of Bmp signalling in regulating its differentiation.

2022-05-01 | GSE201611 | 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