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Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish.
- Source :
-
Scientific reports [Sci Rep] 2021 Sep 30; Vol. 11 (1), pp. 19520. Date of Electronic Publication: 2021 Sep 30. - Publication Year :
- 2021
-
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.<br /> (© 2021. The Author(s).)
- Subjects :
- Animal Fins blood supply
Animal Fins metabolism
Animal Fins ultrastructure
Animals
Biomarkers
Cell Line
Collagen Type IV genetics
Collagen Type IV metabolism
Endothelial Cells
Fibrillar Collagens genetics
Fluorescent Antibody Technique
Gene Expression
Gene Knockdown Techniques
Humans
Wound Healing genetics
Capillaries
Fibrillar Collagens metabolism
Neovascularization, Physiologic drug effects
Regeneration
Zebrafish
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 34593884
- Full Text :
- https://doi.org/10.1038/s41598-021-98852-6