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査読

19 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)689-701
ページ数13
ジャーナルJournal of Cell Biology
195
4
DOI
出版ステータスPublished - 2011 11月 14
外部発表はい

ASJC Scopus subject areas

  • 細胞生物学

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