title: The astrocyte-expressed integrin αvβ8 governs blood vessel sprouting in the developing retina.
abstract: The mouse retina is vascularized after birth when angiogenic blood vessels grow and sprout along a pre-formed latticework of astrocytes. How astrocyte-derived cues control patterns of blood vessel growth and sprouting, however, remains enigmatic. Here, we have used molecular genetic strategies in mice to demonstrate that αvβ8 integrin expressed in astrocytes is essential for neovascularization of the developing retina. Selective ablation of αv or β8 integrin gene expression in astrocytes leads to impaired blood vessel sprouting and intraretinal hemorrhage, particularly during formation of the secondary vascular plexus. These pathologies correlate, in part, with diminished αvβ8 integrin-mediated activation of extracellular matrix-bound latent transforming growth factor βs (TGFβs) and defective TGFβ signaling in vascular endothelial cells, but not astrocytes. Collectively, our data demonstrate that αvβ8 integrin is a component of a paracrine signaling axis that links astrocytes to blood vessels and is essential for proper regulation of retinal angiogenesis.
authors: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Shinya
authors: S
authors: Hirota
authors: Qian
authors: Q
authors: Liu
authors: Hye Shin
authors: HS
authors: Lee
authors: Mohammad G
authors: MG
authors: Hossain
authors: Adam
authors: A
authors: Lacy-Hulbert
authors: Joseph H
authors: JH
authors: McCarty
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005838:Genotype; D015151:Immunoblotting; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication / Q000235:genetics / Q000502:physiology*; D012171:Retinal Vessels / Q000196:embryology*
chemical_list: D017931:DNA Primers; D016023:Integrins; C403414:integrin alphavbeta8