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Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye

Successful transition from embryonic to adult circulation is critical for survival of mammalian organisms. This shift occurs in the central cardiovascular circulation and in the eye as oxygen tension increases. However, its regulation is not well understood. We have used combinatorial gene deletion...

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Autores principales: Kurihara, Toshihide, Westenskow, Peter D., Krohne, Tim U., Aguilar, Edith, Johnson, Randall S., Friedlander, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257537/
https://www.ncbi.nlm.nih.gov/pubmed/22084310
http://dx.doi.org/10.1083/jcb.201107029
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author Kurihara, Toshihide
Westenskow, Peter D.
Krohne, Tim U.
Aguilar, Edith
Johnson, Randall S.
Friedlander, Martin
author_facet Kurihara, Toshihide
Westenskow, Peter D.
Krohne, Tim U.
Aguilar, Edith
Johnson, Randall S.
Friedlander, Martin
author_sort Kurihara, Toshihide
collection PubMed
description Successful transition from embryonic to adult circulation is critical for survival of mammalian organisms. This shift occurs in the central cardiovascular circulation and in the eye as oxygen tension increases. However, its regulation is not well understood. We have used combinatorial gene deletion and overexpression assays to assess the effect of astrocyte-targeted deletion of von Hippel–Lindau tumor suppressor (Vhl), hypoxia-inducible factor-αs (Hif-αs), and Vegf on the normal regression of the hyaloidal vessels, the fetal ocular circulation system. Astrocytic Vhl deletion induced accelerated hyaloidal regression and subsequent massive secondary outgrowth. Combinatorial gene deletion involving Vhl, Hif-αs, and Vegf genes revealed that HIF-2α/vascular endothelial growth factor signaling induces secondary outgrowth in Vhl mutants. Conversely, HIF-1α regulated macrophage migration inhibitory factor and promoted macrophage infiltration that accelerates hyaloidal vessel regression. The phenotype observed in Vhl mutants strongly resembles human persistent hyperplastic primary vitreous cases and may provide insights into vascular remodeling mechanisms in other systems.
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spelling pubmed-32575372012-05-14 Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye Kurihara, Toshihide Westenskow, Peter D. Krohne, Tim U. Aguilar, Edith Johnson, Randall S. Friedlander, Martin J Cell Biol Research Articles Successful transition from embryonic to adult circulation is critical for survival of mammalian organisms. This shift occurs in the central cardiovascular circulation and in the eye as oxygen tension increases. However, its regulation is not well understood. We have used combinatorial gene deletion and overexpression assays to assess the effect of astrocyte-targeted deletion of von Hippel–Lindau tumor suppressor (Vhl), hypoxia-inducible factor-αs (Hif-αs), and Vegf on the normal regression of the hyaloidal vessels, the fetal ocular circulation system. Astrocytic Vhl deletion induced accelerated hyaloidal regression and subsequent massive secondary outgrowth. Combinatorial gene deletion involving Vhl, Hif-αs, and Vegf genes revealed that HIF-2α/vascular endothelial growth factor signaling induces secondary outgrowth in Vhl mutants. Conversely, HIF-1α regulated macrophage migration inhibitory factor and promoted macrophage infiltration that accelerates hyaloidal vessel regression. The phenotype observed in Vhl mutants strongly resembles human persistent hyperplastic primary vitreous cases and may provide insights into vascular remodeling mechanisms in other systems. The Rockefeller University Press 2011-11-14 /pmc/articles/PMC3257537/ /pubmed/22084310 http://dx.doi.org/10.1083/jcb.201107029 Text en © 2011 Kurihara et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Kurihara, Toshihide
Westenskow, Peter D.
Krohne, Tim U.
Aguilar, Edith
Johnson, Randall S.
Friedlander, Martin
Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
title Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
title_full Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
title_fullStr Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
title_full_unstemmed Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
title_short Astrocyte pVHL and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye
title_sort astrocyte pvhl and hif-α isoforms are required for embryonic-to-adult vascular transition in the eye
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257537/
https://www.ncbi.nlm.nih.gov/pubmed/22084310
http://dx.doi.org/10.1083/jcb.201107029
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