title: Recombination signal binding protein for Ig-κJ region regulates juxtaglomerular cell phenotype by activating the myo-endocrine program and suppressing ectopic gene expression.
abstract: Recombination signal binding protein for Ig-κJ region (RBP-J), the major downstream effector of Notch signaling, is necessary to maintain the number of renin-positive juxtaglomerular cells and the plasticity of arteriolar smooth muscle cells to re-express renin when homeostasis is threatened. We hypothesized that RBP-J controls a repertoire of genes that defines the phenotype of the renin cell. Mice bearing a bacterial artificial chromosome reporter with a mutated RBP-J binding site in the renin promoter had markedly reduced reporter expression at the basal state and in response to a homeostatic challenge. Mice with conditional deletion of RBP-J in renin cells had decreased expression of endocrine (renin and Akr1b7) and smooth muscle (Acta2, Myh11, Cnn1, and Smtn) genes and regulators of smooth muscle expression (miR-145, SRF, Nfatc4, and Crip1). To determine whether RBP-J deletion decreased the endowment of renin cells, we traced the fate of these cells in RBP-J conditional deletion mice. Notably, the lineage staining patterns in mutant and control kidneys were identical, although mutant kidneys had fewer or no renin-expressing cells in the juxtaglomerular apparatus. Microarray analysis of mutant arterioles revealed upregulation of genes usually expressed in hematopoietic cells. Thus, these results suggest that RBP-J maintains the identity of the renin cell by not only activating genes characteristic of the myo-endocrine phenotype but also, preventing ectopic gene expression and adoption of an aberrant phenotype, which could have severe consequences for the control of homeostasis.
authors.affiliation: Department of Pediatrics, School of Medicine, Department of Biology, Graduate School of Arts and Sciences, and.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Castellanos-Rivera
authors.affiliation: Department of Pediatrics, School of Medicine.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Pentz
authors.affiliation: Department of Pediatrics, School of Medicine, Department of Biology, Graduate School of Arts and Sciences, and.
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Gross
authors.affiliation: Department of Pediatrics, School of Medicine.
authors.forename: Silvia
authors.initials: S
authors.lastname: Medrano
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, Virginia; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, School of Medicine.
authors.forename: Maria Luisa S
authors.initials: ML
authors.lastname: Sequeira-Lopez
authors.affiliation: Department of Pediatrics, School of Medicine, Department of Biology, Graduate School of Arts and Sciences, and rg@virginia.edu.
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
mesh_terms: D000818:Animals; D001665:Binding Sites; D002450:Cell Communication; D019070:Cell Lineage; D049109:Cell Proliferation; D022202:Chromosomes, Artificial, Bacterial; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D007606:Juxtaglomerular Apparatus / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012083:Renin / Q000235:genetics
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D012083:Renin
keywords: cell fate; hematopoiesis; juxtaglomerular cell; renin; smooth muscle