Document Detail


Transcriptional regulator RBP-J regulates the number and plasticity of renin cells.
MedLine Citation:
PMID:  21750232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Ruth M Castellanos Rivera; Maria C Monteagudo; Ellen S Pentz; Sean T Glenn; Kenneth W Gross; Oscar Carretero; Maria Luisa S Sequeira-Lopez; R Ariel Gomez
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-07-12
Journal Detail:
Title:  Physiological genomics     Volume:  43     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-09     Completed Date:  2012-01-09     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1021-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Genotype
Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics,  metabolism*
Immunohistochemistry
Juxtaglomerular Apparatus / cytology,  metabolism
Mice
Mice, Knockout
RNA, Messenger / genetics
Renin / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / genetics,  physiology
Grant Support
ID/Acronym/Agency:
CA-016056/CA/NCI NIH HHS; DK-075481/DK/NIDDK NIH HHS; R01HL-096735/HL/NHLBI NIH HHS; R37HL-066242/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Immunoglobulin J Recombination Signal Sequence-Binding Protein; 0/RNA, Messenger; 0/Rbpj protein, mouse; EC 3.4.23.15/Renin
Comments/Corrections

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