PUBLICATION
Spatiotemporal modulation of nitric oxide and Notch signaling by hemodynamic-responsive Trpv4 is essential for ventricle regeneration
- Authors
- Yu, C., Li, X., Ma, J., Liang, S., Zhao, Y., Li, Q., Zhang, R.
- ID
- ZDB-PUB-240128-6
- Date
- 2024
- Source
- Cellular and molecular life sciences : CMLS 81: 6060 (Journal)
- Registered Authors
- Zhang, Ruilin
- Keywords
- Heart regeneration, Hemodynamics, NO signal, TGF-β, Trpv4
- MeSH Terms
-
- Animals
- Endocardium/metabolism
- Heart
- Hemodynamics
- Nitric Oxide*/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38279064 Full text @ Cell. Mol. Life Sci.
Citation
Yu, C., Li, X., Ma, J., Liang, S., Zhao, Y., Li, Q., Zhang, R. (2024) Spatiotemporal modulation of nitric oxide and Notch signaling by hemodynamic-responsive Trpv4 is essential for ventricle regeneration. Cellular and molecular life sciences : CMLS. 81:6060.
Abstract
Zebrafish have a remarkable ability to regenerate injured hearts. Altered hemodynamic forces after larval ventricle ablation activate the endocardial Klf2a-Notch signaling cascade to direct zebrafish cardiac regeneration. However, how the heart perceives blood flow changes and initiates signaling pathways promoting regeneration is not fully understood. The present study demonstrated that the mechanosensitive channel Trpv4 sensed the altered hemodynamic forces in injured hearts and its expression was regulated by blood flow. In addition to mediating the endocardial Klf2a-Notch signal cascade around the atrioventricular canal (AVC), we discovered that Trpv4 regulated nitric oxide (NO) signaling in the bulbus arteriosus (BA). Further experiments indicated that Notch signaling primarily acted at the early stage of regeneration, and the major role of NO signaling was at the late stage and through TGF-β pathway. Overall, our findings revealed that mechanosensitive channels perceived the changes in hemodynamics after ventricle injury, and provide novel insights into the temporal and spatial coordination of multiple signaling pathways regulating heart regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping