title: A new role for the renin-angiotensin system in the development of the ureteric bud and renal collecting system.
abstract: The renin-angiotensin system (RAS) plays a critical role in kidney development. Mutations in the genes encoding components of the RAS or pharmacological inhibition of RAS in mice or humans cause a spectrum of congenital abnormalities of the kidney and urinary tract (CAKUT). The observed defects include renal vascular abnormalities, abnormal glomerulogenesis, renal papillary hypoplasia, hydronephrosis, aberrant ureteric bud (UB) budding, duplicated collecting system and renal tubular dysgenesis. Little is known about the potential role of Ang II and its receptors in the morphogenesis of the UB and renal collecting system. This review emphasizes a novel role for the RAS in the development of the UB, collecting ducts and renal medulla. We observe that UB and surrounding stroma express angiotensinogen and Ang II AT1 receptors (AT1R) in vivo. Ang II stimulates UB cell branching in collagen gel cultures in vitro and induces UB morphogenesis in intact whole embryonic metanephroi grown ex vivo. In contrast, treatment of metanephroi with the AT1R antagonist candesartan inhibits UB branching. In addition, Ang II induces tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) in UB cells. Furthermore, Ang II-stimulated UB morphogenesis is abrogated by inhibition of EGFR tyrosine kinase activity. In summary: 1) Ang II, acting via the AT1R, stimulates UB branching; 2) This process depends on tyrosine phosphorylation of the EGFR. Together, these data indicate that cooperation of AT1R and EGFR signaling performs essential functions during renal collecting system development via control of UB branching morphogenesis.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. iiosipi@tulane.edu
authors.forename: Ihor V
authors.initials: IV
authors.lastname: Yosypiv
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000196:embryology*; D009024:Morphogenesis; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D014513:Ureter / Q000196:embryology*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II