PUBLICATION
MicroRNA26 attenuates vascular smooth muscle maturation via endothelial BMP signalling
- Authors
- Watterston, C., Zeng, L., Onabadejo, A., Childs, S.J.
- ID
- ZDB-PUB-191127-12
- Date
- 2019
- Source
- PLoS Genetics 15: e1008163 (Journal)
- Registered Authors
- Childs, Sarah J., Zeng, Lei
- Keywords
- none
- MeSH Terms
-
- Animals
- Bone Morphogenetic Protein Receptors/genetics
- Bone Morphogenetic Protein Receptors/metabolism
- Cell Differentiation
- Endothelial Cells/metabolism*
- Endothelium
- Gene Expression Regulation/genetics
- MicroRNAs/genetics*
- MicroRNAs/metabolism*
- Muscle, Smooth, Vascular/metabolism
- Pulmonary Artery/metabolism
- Signal Transduction/drug effects
- Smad1 Protein/genetics
- Smad1 Protein/metabolism
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- PubMed
- 31091229 Full text @ PLoS Genet.
Citation
Watterston, C., Zeng, L., Onabadejo, A., Childs, S.J. (2019) MicroRNA26 attenuates vascular smooth muscle maturation via endothelial BMP signalling. PLoS Genetics. 15:e1008163.
Abstract
As small regulatory transcripts, microRNAs (miRs) act as genetic 'fine tuners' of posttranscriptional events, and as genetic switches to promote phenotypic switching. The miR miR26a targets the BMP signalling effector, smad1. We show that loss of miR26a leads to hemorrhage (a loss of vascular stability) in vivo, suggesting altered vascular differentiation. Reduction in miR26a levels increases smad1 mRNA and phospho-Smad1 (pSmad1) levels. We show that increasing BMP signalling by overexpression of smad1 also leads to hemorrhage. Normalization of Smad1 levels through double knockdown of miR26a and smad1 rescues hemorrhage, suggesting a direct relationship between miR26a, smad1 and vascular stability. Using an in vivo BMP genetic reporter and pSmad1 staining, we show that the effect of miR26a on smooth muscle differentiation is non-autonomous; BMP signalling is active in embryonic endothelial cells, but not in smooth muscle cells. Nonetheless, increased BMP signalling due to loss of miR26a results in an increase in acta2-expressing smooth muscle cell numbers and promotes a differentiated smooth muscle morphology. Similarly, forced expression of smad1 in endothelial cells leads to an increase in smooth muscle cell number and coverage. Furthermore, smooth muscle phenotypes caused by inhibition of the BMP pathway are rescued by loss of miR26a. Taken together, our data suggest that miR26a modulates BMP signalling in endothelial cells and indirectly promotes a differentiated smooth muscle phenotype. Our data highlights how crosstalk from BMP-responsive endothelium to smooth muscle is important for smooth muscle differentiation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping