title: Transcriptional regulator RBP-J regulates the number and plasticity of renin cells.
abstract: Renin-expressing cells are crucial in the control of blood pressure and fluid-electrolyte homeostasis. Notch receptors convey cell-cell signals that may regulate the renin cell phenotype. Because the common downstream effector for all Notch receptors is the transcription factor RBP-J, we used a conditional knockout approach to delete RBP-J in cells of the renin lineage. The resultant RBP-J conditional knockout (cKO) mice displayed a severe reduction in the number of renin-positive juxtaglomerular apparatuses (JGA) and a reduction in the total number of renin positive cells per JGA and along the afferent arterioles. This reduction in renin protein was accompanied by a decrease in renin mRNA expression, decreased circulating renin, and low blood pressure. To investigate whether deletion of RBP-J altered the ability of mice to increase the number of renin cells normally elicited by a physiological threat, we treated RBP-J cKO mice with captopril and sodium depletion for 10 days. The resultant treated RBP-J cKO mice had a 65% reduction in renin mRNA levels (compared with treated controls) and were unable to increase circulating renin. Although these mice attempted to increase the number of renin cells, the cells were unusually thin and had few granules and barely detectable amounts of immunoreactive renin. As a consequence, the cells were incapable of fully adopting the endocrine phenotype of a renin cell. We conclude that RBP-J is required to maintain basal renin expression and the ability of smooth muscle cells along the kidney vasculature to regain the renin phenotype, a fundamental mechanism to preserve homeostasis.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Castellanos Rivera
authors.forename: Maria C
authors.initials: MC
authors.lastname: Monteagudo
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Pentz
authors.forename: Sean T
authors.initials: ST
authors.lastname: Glenn
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Gross
authors.forename: Oscar
authors.initials: O
authors.lastname: Carretero
authors.forename: Maria Luisa S
authors.initials: ML
authors.lastname: Sequeira-Lopez
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005838:Genotype; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D012333:RNA, Messenger; C497571:Rbpj protein, mouse; D012083:Renin