title: Renin lineage cells repopulate the glomerular mesangium after injury.
abstract: Mesangial cell injury has a major role in many CKDs. Because renin-positive precursor cells give rise to mesangial cells during nephrogenesis, this study tested the hypothesis that the same phenomenon contributes to glomerular regeneration after murine experimental mesangial injury. Mesangiolysis was induced by administration of an anti-mesangial cell serum in combination with LPS. In enhanced green fluorescent protein-reporter mice with constitutively labeled renin lineage cells, the size of the enhanced green fluorescent protein-positive area in the glomerular tufts increased after mesangial injury. Furthermore, we generated a novel Tet-on inducible triple-transgenic LacZ reporter line that allowed selective labeling of renin cells along renal afferent arterioles of adult mice. Although no intraglomerular LacZ expression was detected in healthy mice, about two-thirds of the glomerular tufts became LacZ positive during the regenerative phase after severe mesangial injury. Intraglomerular renin descendant LacZ-expressing cells colocalized with mesangial cell markers α8-integrin and PDGF receptor-β but not with endothelial, podocyte, or parietal epithelial cell markers. In contrast with LacZ-positive cells in the afferent arterioles, LacZ-positive cells in the glomerular tuft did not express renin. These data demonstrate that extraglomerular renin lineage cells represent a major source of repopulating cells for reconstitution of the intraglomerular mesangium after injury.
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany;
authors.forename: Charlotte
authors.initials: C
authors.lastname: Starke
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany;
authors.forename: Hannah
authors.initials: H
authors.lastname: Betz
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany;
authors.forename: Linda
authors.initials: L
authors.lastname: Hickmann
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Lachmann
authors.affiliation: Institute of Physiology, University of Regensburg, Regensburg, Germany;
authors.forename: Björn
authors.initials: B
authors.lastname: Neubauer
authors.affiliation: Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
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.
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany;
authors.forename: Bernd
authors.initials: B
authors.lastname: Hohenstein
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; christian.hugo@uniklinikum-dresden.de vladimir.todorov@uniklinikum-dresden.de.
authors.forename: Vladimir T
authors.initials: VT
authors.lastname: Todorov
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany;
authors.forename: Christian P M
authors.initials: CP
authors.lastname: Hugo
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D004318:Doxycycline / Q000008:administration & dosage; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D017930:Genes, Reporter; D005920:Glomerular Mesangium / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007668:Kidney / Q000293:injuries*; D007678:Kidney Glomerulus / Q000378:metabolism; D007763:Lac Operon; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012083:Renin / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology
chemical_list: D008070:Lipopolysaccharides; D049452:Green Fluorescent Proteins; D004656:Enalapril; D012083:Renin; D004318:Doxycycline
keywords: glomerular disease; mesangial cells; stem cell