Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease

• Published in: American journal of physiology. Renal physiology Vol. 309; no. 4; pp. F341 - F358
• Main Authors: Pippin, Jeffrey W, Kaverina, Natalya V, Eng, Diana G, Krofft, Ronald D, Glenn, Sean T, Duffield, Jeremy S, Gross, Kenneth W, Shankland, Stuart J
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.08.2015
• Subjects: Adult Stem Cells - metabolism; Adult Stem Cells - ultrastructure; Animals; Biomarkers - metabolism; Cell Differentiation; Cell Lineage; Cell Movement; Cells; Disease Models, Animal; Gene Expression Regulation; Genes, Reporter; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - metabolism; Glomerulosclerosis, Focal Segmental - pathology; Kidney diseases; Kidney Glomerulus - metabolism; Kidney Glomerulus - ultrastructure; Luminescent Proteins - biosynthesis; Luminescent Proteins - genetics; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Nephritis, Interstitial - genetics; Nephritis, Interstitial - metabolism; Nephritis, Interstitial - pathology; Pericytes - metabolism; Pericytes - ultrastructure; Phenotype; Pluripotent Stem Cells - metabolism; Pluripotent Stem Cells - ultrastructure; Podocytes - metabolism; Podocytes - ultrastructure; Protein expression; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; Renin - genetics; Renin - metabolism; Rodents; interstitium; pericyte; regeneration; PDGFβ-R; podocyte; tubulointerstitium; FSGS; remnant kidney
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00438.2014

Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease.