PUBLICATION
BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice
- Authors
- Bongiovanni, C., Bueno-Levy, H., Posadas Pena, D., Del Bono, I., Miano, C., Boriati, S., Da Pra, S., Sacchi, F., Redaelli, S., Bergen, M., Romaniello, D., Pontis, F., Tassinari, R., Kellerer, L., Petraroia, I., Mazzeschi, M., Lauriola, M., Ventura, C., Heermann, S., Weidinger, G., Tzahor, E., D'Uva, G.
- ID
- ZDB-PUB-240429-1
- Date
- 2024
- Source
- Cell Reports 43: 114162114162 (Journal)
- Registered Authors
- Heermann, Stephan, Weidinger, Gilbert
- Keywords
- AKT, BMP7, CP: Developmental biology, CP: Stem cell research, ERK, SMAD5, cardiac injuries, cardiomyocyte proliferation, heart regeneration, mice, regenerative growth factors, zebrafish
- MeSH Terms
-
- Mice
- Bone Morphogenetic Protein Receptors, Type I/genetics
- Bone Morphogenetic Protein Receptors, Type I/metabolism
- Smad5 Protein/metabolism
- Mice, Inbred C57BL
- Regeneration*
- Cell Proliferation*
- Animals
- Signal Transduction
- Myocardial Infarction/metabolism
- Myocardial Infarction/pathology
- Bone Morphogenetic Protein 7*/genetics
- Bone Morphogenetic Protein 7*/metabolism
- Zebrafish*/metabolism
- Neuregulin-1/genetics
- Neuregulin-1/metabolism
- Myocytes, Cardiac*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38678558 Full text @ Cell Rep.
Citation
Bongiovanni, C., Bueno-Levy, H., Posadas Pena, D., Del Bono, I., Miano, C., Boriati, S., Da Pra, S., Sacchi, F., Redaelli, S., Bergen, M., Romaniello, D., Pontis, F., Tassinari, R., Kellerer, L., Petraroia, I., Mazzeschi, M., Lauriola, M., Ventura, C., Heermann, S., Weidinger, G., Tzahor, E., D'Uva, G. (2024) BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice. Cell Reports. 43:114162114162.
Abstract
Zebrafish have a lifelong cardiac regenerative ability after damage, whereas mammals lose this capacity during early postnatal development. This study investigated whether the declining expression of growth factors during postnatal mammalian development contributes to the decrease of cardiomyocyte regenerative potential. Besides confirming the proliferative ability of neuregulin 1 (NRG1), interleukin (IL)1b, receptor activator of nuclear factor kappa-Β ligand (RANKL), insulin growth factor (IGF)2, and IL6, we identified other potential pro-regenerative factors, with BMP7 exhibiting the most pronounced efficacy. Bmp7 knockdown in neonatal mouse cardiomyocytes and loss-of-function in adult zebrafish during cardiac regeneration reduced cardiomyocyte proliferation, indicating that Bmp7 is crucial in the regenerative stages of mouse and zebrafish hearts. Conversely, bmp7 overexpression in regenerating zebrafish or administration at post-mitotic juvenile and adult mouse stages, in vitro and in vivo following myocardial infarction, enhanced cardiomyocyte cycling. Mechanistically, BMP7 stimulated proliferation through BMPR1A/ACVR1 and ACVR2A/BMPR2 receptors and downstream SMAD5, ERK, and AKT signaling. Overall, BMP7 administration is a promising strategy for heart regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping