PUBLICATION
Crip2 affects vascular development by fine-tuning endothelial cell aggregation and proliferation
- Authors
- Yang, S., Zhang, X., Li, X., Li, H.
- ID
- ZDB-PUB-250313-32
- Date
- 2025
- Source
- Cellular and molecular life sciences : CMLS 82: 110110 (Journal)
- Registered Authors
- Li, Hongyan
- Keywords
- Cell aggregation, Cell proliferation, Crip2, Vascular development
- MeSH Terms
-
- Signal Transduction*
- Animals
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- cdc42 GTP-Binding Protein/genetics
- cdc42 GTP-Binding Protein/metabolism
- Cell Aggregation
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Serum Response Factor/genetics
- Serum Response Factor/metabolism
- Human Umbilical Vein Endothelial Cells*/metabolism
- Cell Movement*/genetics
- Endothelial Cells/cytology
- Endothelial Cells/metabolism
- Cell Proliferation*
- LIM Domain Proteins/genetics
- LIM Domain Proteins/metabolism
- Neovascularization, Physiologic/genetics
- Humans
- Cell Adhesion/genetics
- PubMed
- 40074973 Full text @ Cell. Mol. Life Sci.
Citation
Yang, S., Zhang, X., Li, X., Li, H. (2025) Crip2 affects vascular development by fine-tuning endothelial cell aggregation and proliferation. Cellular and molecular life sciences : CMLS. 82:110110.
Abstract
Endothelial cell adhesion and migration are crucial to various biological processes, including vascular development. The identification of factors that modulate vascular development through these cell functions has emerged as a prominent focus in cardiovascular research. Crip2 is known to play a crucial role in cardiac development, yet its involvement in vascular development and the underlying mechanism remains elusive. In this study, we revealed that Crip2 is expressed predominantly in the vascular system, particularly in the posterior cardinal vein and caudal vein plexus intersegmental vein. Upon Crip2 loss, the posterior cardinal vein plexus and caudal vein plexus are hypoplastic, and endothelial cells exhibit aberrant aggregation. In human umbilical vein endothelial cells (HUVECs), CRIP2 interacts with the cytoskeleton proteins KRT8 and VIM. The absence of CRIP2 negatively regulates their expression, thereby fine-tuning cytoskeleton formation, resulting in a hyperadhesive phenotype. Moreover, CRIP2 deficiency perturbs the VEGFA/CDC42 signaling pathway, which in turn diminishes the migrating capacity of HUVECs. Furthermore, the loss of CRIP2 impairs cell proliferation by affecting its interaction with SRF through PDE10A/cAMP and PDGF/JAK/STAT/SRF signaling. Collectively, our findings delineate a crucial role for CRIP2 in controlling the migration, adhesion and proliferation of endothelial cells, thereby contributing to vascular development in zebrafish. These insights may provide a deeper understanding of the etiology of cardiovascular disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping