PUBLICATION
The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration
- Authors
- Goumenaki, P., Günther, S., Kikhi, K., Looso, M., Marín-Juez, R., Stainier, D.Y.R.
- ID
- ZDB-PUB-240915-7
- Date
- 2024
- Source
- Nature cardiovascular research 3: 115811761158-1176 (Journal)
- Registered Authors
- Marín-Juez, Rubén, Stainier, Didier
- Keywords
- none
- Datasets
- GEO:GSE262169, GEO:GSE262351, GEO:GSE262247, GEO:GSE262248
- MeSH Terms
-
- Fibrosis*
- Signal Transduction*
- Neutrophils/immunology
- Neutrophils/metabolism
- Regeneration*/genetics
- PubMed
- 39271818 Full text @ Nat Cardiovasc Res
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.
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