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.