Ontogeny of Bradykinin B1 Receptors in the Mouse Kidney

Abstract

Kinins are vasoactive peptides that stimulate two G-protein coupled bradykinin receptors (B1R and B2R). B2R-knockout mice are salt sensitive and develop renal dysgenesis and hypertension if salt stressed during embryogenesis. B1R-knockout mice, on the other hand, are protected from inflammation and fibrosis. This study examined the spatiotemporal expression of B1R during renal organogenesis. The segmental nephron identity of B1R immunoreactivity was determined by costaining with markers of the collecting duct (Dolichos biflorus), proximal tubule (Dolichos tetraglonus), and nephron progenitors (Pax2). At E14.5, the B1R was confined to few cells in the metanephric mesenchyme. Abundance of B1R increased progressively during development. On E17.5, B1R was enriched in differentiating proximal tubular cells and by postnatal day 1, B1R was clearly expressed on the luminal aspect of the proximal tubule. Quantitative real-time PCR revealed that the levels of B1R mRNA more than double during renal maturation. We conclude that 1) B1R expression correlates closely with nephron maturation; 2) lack of B1R in nephron progenitors suggests that B1R is unlikely to play a role in early nephrogenesis; and 3) enrichment of B1R in maturing proximal tubule suggests a potential role for this receptor in terminal differentiation of the proximal nephron.