title: Loss of Jagged1 in renin progenitors leads to focal kidney fibrosis.
abstract: The Notch signaling pathway is required to maintain renin expression within juxtaglomerular (JG) cells. However, the specific ligand which activates Notch signaling in renin-expressing cells remains undefined. In this study, we found that among all Notch ligands, Jagged1 is differentially expressed in renin cells with higher expression during neonatal life. We therefore hypothesized that Jagged1 was involved in renin expression and/or vascular integrity. We used a conditional knockout approach to delete Jagged1 in cells of the renin lineage. Deletion of Jagged1 specifically within renin cells did not result in decreased renin production within the kidney. However, animals with conditional deletion of Jagged1 did develop focal kidney fibrosis and elevated blood urea nitrogen. Our data demonstrate that Jagged1-mediated Notch signaling is dispensable in renin cells of the kidney in regard to renin expression. However, deletion of Jagged1 in renin cells descendants affects perivascular-interstitial integrity leading to focal fibrosis and diminished renal function.
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Belyea
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: Maria Luisa S
authors.initials: ML
authors.lastname: Sequeira-Lopez
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia rg@virginia.edu.
authors.forename: R
authors.initials: R
authors.lastname: Ariel Gomez
keywords: jagged1; notch; renin