Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish

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...

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Autores principales:	Anita Senk, Valentin Djonov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2311c9d6e540467eb36fc9eea92905c4
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spelling	oai:doaj.org-article:2311c9d6e540467eb36fc9eea92905c42021-12-02T17:18:21ZCollagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish10.1038/s41598-021-98852-62045-2322https://doaj.org/article/2311c9d6e540467eb36fc9eea92905c42021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98852-6https://doaj.org/toc/2045-2322Abstract 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.Anita SenkValentin DjonovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anita Senk Valentin Djonov Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
description	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.
format	article
author	Anita Senk Valentin Djonov
author_facet	Anita Senk Valentin Djonov
author_sort	Anita Senk
title	Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
title_short	Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
title_full	Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
title_fullStr	Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
title_full_unstemmed	Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
title_sort	collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2311c9d6e540467eb36fc9eea92905c4
work_keys_str_mv	AT anitasenk collagenfibersprovideguidancecuesforcapillaryregrowthduringregenerativeangiogenesisinzebrafish AT valentindjonov collagenfibersprovideguidancecuesforcapillaryregrowthduringregenerativeangiogenesisinzebrafish
_version_	1718381073207918592

Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish

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