title: Cell-cycle mechanisms involved in podocyte proliferation in cellular lesion of focal segmental glomerulosclerosis.
abstract: BACKGROUND
  Podocyte injury may induce podocyte proliferation, which results in glomerular scarring. The cellular lesion, seen in some patients with primary focal segmental glomerulosclerosis (FSGS), is characterized by proliferation of cells covering the sclerotic or collapsed glomerular tufts. Cell-cycle mechanisms by which podocyte proliferation occurs in the cellular lesion of FSGS are unclear.
  
  
  METHODS
  We examined expression patterns of cyclin D1; cyclin E; cyclin A; cyclin B1; cyclin-dependent kinase (CDK)2; CDK4; such CDK inhibitors as p21WAF1/CIP1 (p21), p27kip1 (p27), and p57kip2 (p57); and Wilms' tumor protein-1 (WT-1) in 12 renal biopsy specimens with the cellular lesion of FSGS and 6 renal biopsy specimens with no detectable abnormalities by immunohistochemistry and immunoelectron microscopy. Messenger RNA (mRNA) expression patterns of cyclin D1, cyclin E, p21, p27, and p57 were evaluated further by in situ hybridization.
  
  
  RESULTS
  In controls, immunostaining for cyclin A, cyclin B1, CDK2, CDK4, and p21 was almost negligible, but positive signals for cyclin D1, cyclin E, p27, and p57 were observed in glomerular epithelial cells (GECs). In the cellular lesion of FSGS, positive signals for cyclin E, cyclin A, cyclin B1, CDK2, and p21 were present in GEC nuclei, in which WT-1, p27, p57, and cyclin D1 were undetected. Immunoelectron microscopy showed that cyclin E-, CDK2-, and p21-specific gold particles were increased significantly in GEC nuclei in the cellular lesion in which cyclin D- and p57-specific particles were absent compared with controls. An in situ hybridization study showed specific signals of cyclin D1, cyclin E, p21, p27, and p57 mRNA in GECs forming the cellular lesion of FSGS.
  
  
  CONCLUSIONS
  Our results suggest that damaged podocytes may inhibit p27 and p57 protein expression, but activate a cyclin D1-independent cell-cycle mechanism and mitotic cell cyclins to promote GEC proliferation in the cellular lesion of FSGS.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Suxia
authors.initials: S
authors.lastname: Wang
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Moon
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Hong
authors.forename: Hyun Soon
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002453:Cell Cycle; D002455:Cell Division; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000166:cytology*; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged
chemical_list: D016213:Cyclins; D018844:Cyclin-Dependent Kinases