Reference - Detail
| RRC ID | 85675 |
|---|---|
| Author | Wang ZY, Mehra A, Wang QC, Gupta S, Ribeiro da Silva A, Juan T, Günther S, Looso M, Detleffsen J, Stainier DYR, Marín-Juez R. |
| Title | flt1 inactivation promotes zebrafish cardiac regeneration by enhancing endothelial activity and limiting the fibrotic response. |
| Journal | Development |
| Abstract |
VEGFA administration has been explored as a pro-angiogenic therapy for cardiovascular diseases including heart failure for several years, but with little success. Here, we investigate a different approach to augment VEGFA bioavailability: by deleting the VEGFA decoy receptor VEGFR1 (also known as FLT1), one can achieve more physiological VEGFA concentrations. We find that after 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 these beneficial effects of flt1 deletion. Transcriptomic analyses of cryoinjured flt1 mutant hearts reveal enhanced endothelial MAPK/ERK signaling and downregulation of the transcription factor gene egr3. Using newly generated genetic tools, we observe egr3 upregulation in the regenerating endocardium, and find that Egr3 promotes myofibroblast differentiation. These data indicate that with enhanced Vegfa bioavailability, the endocardium limits myofibroblast differentiation via egr3 downregulation, thereby providing a more permissive microenvironment for cardiomyocyte replenishment after injury. |
| Volume | 151(23) |
| Published | 2024-12-1 |
| DOI | 10.1242/dev.203028 |
| PII | 363231 |
| PMID | 39612288 |
| PMC | PMC11634031 |
| MeSH | Animals Cell Differentiation* / genetics Cell Proliferation / genetics Early Growth Response Protein 3 / genetics Early Growth Response Protein 3 / metabolism Endocardium / metabolism Endocardium / pathology Fibrosis Heart* Myocytes, Cardiac* / metabolism Myofibroblasts / metabolism Neovascularization, Physiologic / genetics Regeneration* / genetics Signal Transduction / genetics Vascular Endothelial Growth Factor A* / genetics Vascular Endothelial Growth Factor A* / metabolism Vascular Endothelial Growth Factor Receptor-1* / genetics Vascular Endothelial Growth Factor Receptor-1* / metabolism Zebrafish* Zebrafish Proteins* / genetics Zebrafish Proteins* / metabolism |
| IF | 5.611 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Bluesky |
| Total number of mentions | 29 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Zebrafish | UAS:GFP |