| First Author | Castellanos-Rivera RM | Year | 2015 |
| Journal | J Am Soc Nephrol | Volume | 26 |
| Issue | 1 | Pages | 67-80 |
| PubMed ID | 24904090 | Mgi Jnum | J:316811 |
| Mgi Id | MGI:6832410 | Doi | 10.1681/ASN.2013101045 |
| Citation | Castellanos-Rivera RM, et al. (2015) Recombination signal binding protein for Ig-kappaJ region regulates juxtaglomerular cell phenotype by activating the myo-endocrine program and suppressing ectopic gene expression. J Am Soc Nephrol 26(1):67-80 |
| abstractText | Recombination signal binding protein for Ig-kappaJ 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. |
