title: Angiopoietin-2 is a site-specific factor in differentiation of mouse renal vasculature.
abstract: Angiopoietin-1 (Ang-1) stimulates endothelial and vascular network differentiation through the Tie-2 receptor tyrosine kinase, while Ang-2 modulates this activation in embryo and tumor growth. The nephrogenic pattern of Ang-2 was documented in a mouse strain that expresses the LacZ reporter gene driven by the Ang-2 promoter. Heterozygous animals were healthy with morphologically normal kidneys, and they were examined after X-gal staining. At embryonic days 10.5 (E10.5) and E12.0, transgene expression was absent in the mesonephros and metanephros. At E14.0, expression was noted in the metanephric artery and its major branches. At E19.0 and in neonatal kidneys, expression was maintained in larger renal artery branches, extending to arcuate and smaller cortical vessels. Histologically, transgene expression was located in multiple layers of vessel wall cells, extending further from the endothelium than alpha-smooth muscle actin. The mesangium of immature glomeruli also expressed LacZ. In the first 3 postnatal weeks, a new pattern became evident, with intense X-gal staining in the inner stripe of the outer medulla, where a subset of thin descending limbs of loops of Henle expressed the transgene. This dynamic and developmentally regulated pattern indicates that Ang-2 is an early marker of the renal pericyte and vascular smooth muscle lineage and is also an epithelial-derived growth factor. Because Tie-2 is widely expressed by differentiating renal endothelia, this study is consistent with the hypothesis that Ang-2 has roles in kidney vascular maturation.
authors.affiliation: Nephrourology Unit, Institute of Child Health, University College London Medical School, London, United Kingdom.
authors.forename: Hai Tao
authors.initials: HT
authors.lastname: Yuan
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Chitra
authors.initials: C
authors.lastname: Suri
authors.affiliation: Department of Clinical Neurology, Institute of Neurology, University College London Medical School, London, United Kingdom.
authors.forename: David N
authors.initials: DN
authors.lastname: Landon
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Nephrourology Unit, Institute of Child Health, University College London Medical School, London, United Kingdom.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf
mesh_terms: D042702:Angiopoietin-2; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D007763:Lac Operon; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012077:Renal Artery / Q000196:embryology*; D012082:Renal Veins / Q000196:embryology*; D013194:Staining and Labeling / Q000379:methods
chemical_list: D042702:Angiopoietin-2; D011506:Proteins; D020794:Receptor Protein-Tyrosine Kinases