イシズ　アヤコ   Ayako Nakamura-Ishizu   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The formation of an angiogenic astrocyte template is regulated by the neuroretina in a HIF-1-dependent manner.
掲載誌名	正式名：Developmental biology 略　 称：Dev Biol ISSNコード：1095564X/00121606
掲載区分	国外
巻・号・頁	363(1),pp.106-14
著者・共著者	Nakamura-Ishizu Ayako, Kurihara Toshihide, Okuno Yuji, Ozawa Yoko, Kishi Kazuo, Goda Nobuhito, Tsubota Kazuo, Okano Hideyuki, Suda Toshio, Kubota Yoshiaki
発行年月	2012/03
概要	The vascular and nervous systems display a high degree of cross-talk and depend on each other functionally. In the vascularization of the central nervous system, astrocytes have been thought to sense tissue oxygen levels in hypoxia-inducible factors (HIFs)-dependent manner and control the vascular growth into the hypoxic area by secreting VEGF. However, recent genetic evidences demonstrate that not only astrocyte HIFs but also astrocyte VEGF expression is dispensable for developmental angiogenesis of the retina. This study demonstrates that hypoxia-inducible factor 1 alpha subunit (HIF-1α), a key transcription factor involved in cellular responses to hypoxia, is most abundantly expressed in the neuroretina, especially retinal progenitor cells (RPCs). A neuroretina-specific knockout of HIF-1α (αCre(+)Hif1α(flox/flox)) showed impaired vascular development characterized by decreased tip cell filopodia and reduced vessel branching. The astrocyte network was hypoplastic in αCre(+)Hif1α(flox/flox) mice. Mechanistically, platelet-derived growth factor A (PDGF-A), a mitogen for astrocytes, was downregulated in the neuroretina of αCre(+)Hif1α(flox/flox) mice. Supplementing PDGF-A restored reduced astrocytic and vascular density in αCre(+)Hif1α(flox/flox) mice. Our data demonstrates that the neuroretina but not astrocytes acts as a primary oxygen sensor which ultimately controls the retinal vascular development by regulating an angiogenic astrocyte template.
DOI	10.1016/j.ydbio.2011.12.027
PMID	22226979