PUBLICATION
Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
- Authors
- Senk, A., Djonov, V.
- ID
- ZDB-PUB-211002-3
- Date
- 2021
- Source
- Scientific Reports 11: 19520 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animal Fins/blood supply
- Animal Fins/metabolism
- Animal Fins/ultrastructure
- Animals
- Biomarkers
- Capillaries*
- Cell Line
- Collagen Type IV/genetics
- Collagen Type IV/metabolism
- Endothelial Cells
- Fibrillar Collagens/genetics
- Fibrillar Collagens/metabolism*
- Fluorescent Antibody Technique
- Gene Expression
- Gene Knockdown Techniques
- Humans
- Neovascularization, Physiologic*/drug effects
- Regeneration*
- Wound Healing/genetics
- Zebrafish*
- PubMed
- 34593884 Full text @ Sci. Rep.
Citation
Senk, A., Djonov, V. (2021) Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish. Scientific Reports. 11:19520.
Abstract
Although well investigated, the importance of collagen fibers in supporting angiogenesis is not well understood. In this study, we demonstrate that extracellular collagen fibers provide guidance cues for endothelial cell migration during regenerative angiogenesis in the caudal zebrafish fin. Inhibition of collagen cross-linking by β-Aminopropionitrile results in a 70% shorter regeneration area with 50% reduced vessel growth and disintegrated collagen fibers. The disrupted collagen scaffold impedes endothelial cell migration and induces formation of abnormal angioma-like blood vessels. Treatment of the Fli//colRN zebrafish line with the prodrug Nifurpirinol, which selectively damages the active collagen-producing 1α2 cells, reduced the regeneration area and vascular growth by 50% with wider, but less inter-connected, capillary segments. The regenerated area contained larger vessels partially covered by endothelial cells embedded in atypical extracellular matrix containing cell debris and apoptotic bodies, macrophages and granulocytes. Similar experiments performed in early embryonic zebrafish suggested that collagens are important also during embryonic angiogenesis. In vitro assays revealed that collagen I allows for the most efficient endothelial cell migration, followed by collagen IV relative to the complete absence of exogenous matrix support. Our data demonstrates severe vascular defects and restricted fin regeneration when collagens are impaired. Collagen I therefore, provides support and guidance for endothelial cell migration while collagen IV is responsible for proper lumen formation and vascular integrity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping