title: Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies.
abstract: BACKGROUND
  Mature podocytes are growth-arrested because of the expression of cyclin-dependent kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a dysregulation of their differentiated phenotype and proliferate.
  
  
  METHODS
  To shed light on the mechanism underlying podocyte proliferation in CG, we analyzed the expression of the proliferation marker Ki-67, cyclins (A, D1), cyclin-dependent kinase inhibitors (p27, p57), and podocyte differentiation marker synaptopodin in eight cases of HIVAN and two cases of idiopathic CG. Normal fetal and adult kidneys served as controls.
  
  
  RESULTS
  Both HIVAN and idiopathic CG showed a marked reduction in the expression of p27, p57, and cyclin D1 (absent in 69, 62, and 80% of all glomeruli, respectively). Cyclin A and Ki-67 were expressed in 11 and 29% of all glomeruli. Moreover, there was partial loss of synaptopodin and cyclin D1 expression in nonaffected glomeruli.
  
  
  CONCLUSIONS
  The loss of p27 and p57 leading to expression of cyclin A may account for the activation of podocyte proliferation in CG. Furthermore, the loss of cyclin D1 from histologically normal glomeruli suggests a possible role of cyclin D1 in mediating the dysregulation of the podocyte cell cycle in CG. These novel findings offer insight into the molecular regulation of mature podocyte differentiation. Podocyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.
authors.affiliation: Department of Pathology, New York University, New York 10016, USA. barisoni@yahoo.com
authors.forename: L
authors.initials: L
authors.lastname: Barisoni
authors.forename: M
authors.initials: M
authors.lastname: Mokrzycki
authors.forename: L
authors.initials: L
authors.lastname: Sablay
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: H
authors.initials: H
authors.lastname: Yamase
authors.forename: P
authors.initials: P
authors.lastname: Mundel
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000473:pathology*; D000328:Adult; D000367:Age Factors; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019925:Cyclin A / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D019938:Cyclin D1 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003560:Cysts / Q000473:pathology; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000032:analysis / Q000276:immunology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D009124:Muscle Proteins; D038941:Polypyrimidine Tract-Binding Protein; D016601:RNA-Binding Proteins / Q000032:analysis / Q000276:immunology; D012261:Ribonucleoproteins / Q000032:analysis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D019925:Cyclin A; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D009124:Muscle Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C503967:SYNPO protein, human; C503968:Synpo protein, mouse; C058992:Tagln protein, mouse; D019938:Cyclin D1; D038941:Polypyrimidine Tract-Binding Protein; D018844:Cyclin-Dependent Kinases