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

Toshihide Kurihara, Peter D. Westenskow, Tim U. Krohne, Edith Aguilar, Randall S. Johnson, Martin Friedlander

研究成果: Article

18 引用 (Scopus)

抜粋

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), hypoxiainducible 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.

元の言語English
ページ(範囲)689-701
ページ数13
ジャーナルJournal of Cell Biology
195
発行部数4
DOI
出版物ステータスPublished - 2011 11 14
外部発表Yes

ASJC Scopus subject areas

  • Cell Biology

フィンガープリント Astrocyte pvhl and HIF-α isoforms are required for embryonic-to-adult vascular transition in the eye' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用