Renin lineage cells repopulate the glomerular mesangium after injury.
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.
['Starke|Charlotte|C|', 'Betz|Hannah|H|', 'Hickmann|Linda|L|', 'Lachmann|Peter|P|', 'Neubauer|Björn|B|', 'Kopp|Jeffrey B|JB|', 'Sequeira-Lopez|Maria Luisa S|ML|', 'Gomez|R Ariel|RA|', 'Hohenstein|Bernd|B|', 'Todorov|Vladimir T|VT|', 'Hugo|Christian P M|CP|']
D000818:Animals D030801:Animals, Genetically Modified D019070:Cell Lineage D004318:Doxycycline D004656:Enalapril D005260:Female D017930:Genes, Reporter D005920:Glomerular Mesangium D049452:Green Fluorescent Proteins D021621:Imaging, Three-Dimensional D007668:Kidney D007678:Kidney Glomerulus D007763:Lac Operon D008070:Lipopolysaccharides D008297:Male D051379:Mice D008822:Mice, Transgenic D012083:Renin D013234:Stem Cells
mesangial cells glomerular disease stem cell