The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration.
Nat Cardiovasc Res
; 3(9): 1158-1176, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39271818
ABSTRACT
The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration; however, 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 and 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-of-function and gain-of-function tools, we 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regeneración
/
Fibrosis
/
Pez Cebra
/
Transducción de Señal
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Proteínas de Pez Cebra
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Factor 88 de Diferenciación Mieloide
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Inmunidad Innata
Límite:
Animals
Idioma:
En
Revista:
Nat Cardiovasc Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido