title: Mice are unable to endogenously regenerate podocytes during the repair of immunotoxin-induced glomerular injury.
abstract: BACKGROUND
  Recent studies have reported that podocytes are postnatally generated from progenitor cells localized in Bowman's capsule or in the bone marrow. In the present study, we investigated whether or not podocyte regeneration is important in the repair of injured glomeruli after mild podocyte injury in mice.
  
  
  METHODS
  Mild podocyte injury was induced in NEP25 mice (n = 8) by injecting an immunotoxin, LMB2 (0.625 ng/g body weight). Control mice, not injured by LMB2 injection (n = 7) was used as a comparison. Proliferating cells were labeled by continuous infusion of bromodeoxyuridine (BrdU). Podocytes, identified by nephrin, WT1 or podocin staining, that had incorporated BrdU were enumerated 4 weeks later.
  
  
  RESULTS
  A total of 742 corpuscles were inspected in serial sections stained for BrdU and nephrin; 19% showed sclerosis. BrdU(+) cells were observed in both the glomeruli and Bowman's capsules, averaging 2.5 ± 3.1 in non-sclerotic corpuscles and 7.0 ± 5.8 in sclerotic corpuscles. Only one BrdU(+) cell was also positive for nephrin. Another cell, localized at a position consistent with its potential identification as a podocyte, was nephrin negative but had incorporated BrdU. WT1 staining similarly revealed that only two nuclei were doubly positive for BrdU and WT1. Additional 1676 corpuscles were inspected by double staining for BrdU and podocin; none were doubly positive.
  
  
  CONCLUSIONS
  Podocytes are not replenished by proliferation of endogenous progenitor cells in mice with glomerular injury.
authors: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors: Yoichi
authors: Y
authors: Miyazaki
authors: Akihiro
authors: A
authors: Shimizu
authors: Iekuni
authors: I
authors: Ichikawa
authors: Tatsuo
authors: T
authors: Hosoya
authors: Ira
authors: I
authors: Pastan
authors: Taiji
authors: T
authors: Matsusaka
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D000922:Immunotoxins / Q000633:toxicity*; D053645:Interleukin-2 Receptor alpha Subunit / Q000502:physiology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D000922:Immunotoxins; D053645:Interleukin-2 Receptor alpha Subunit
keywords: chronic renal failure; glomerulosclerosis; mouse model; podocyte; regeneration