title: Cell-cycle regulatory proteins in the podocyte in collapsing glomerulopathy in children.
abstract: Podocyte is a terminally committed cell in G1 arrest of cell cycle, and is unable to overcome G1/S transition phase in children with minimal change disease (MCD) and classic focal segmental glomerulosclerosis (FSGS), in contrast to dysregulated proliferative phenotype of idiopathic collapsing glomerulopathy (CGN) in adults. Forty-two kidney biopsies, MCD (14), FSGS (12), CGN (4), and normal (CON) (12), were evaluated by immunohistochemistry using dual staining for expression of p27, p21, and p57, and cyclins D and A, in podocytes of children with CGN. On light microscopy, all podocytes expressed p27, whereas p21 and p57 expression was seen in a portion of podocytes in normal kidney biopsies. Cyclin D was expressed in a small percentage of podocytes. Cyclin A expression was absent in normal biopsies. The staining for p27 decreased significantly, in order, from normal (100%) to MCD (45.8%) to CGN (24.2%) to FSGS (16.6%). p21 staining was significantly decreased from normal (69.8%) to CGN (15.5%) to MCD (2.2%) to FSGS (0.6%), and the difference between CGN and MCD and FSGS was also significant. There was no significant difference in staining of p57. Cyclin D staining was significantly increased in CGN (26.8%) compared to normal (7.2%), MCD (1.6%), and FSGS (0.0%), and the difference between CGN and MCD and FSGS was also significant. De novo cyclin A staining was only observed in children with CGN. Thus, p27 and p21 but not p57 was decreased in CGN, as in FSGS when compared to normal. Both cyclins D and A staining were increased in CGN. The staining pattern in CGN would suggest that podocyte is able to overcome G1/S transition phase, and has a proliferative phenotype. We propose, based on the significant contrast observed in podocytes injury response between CGN (proliferative) and classic FSGS (non-proliferative), that CGN not be considered as a morphological variant of FSGS.
authors.affiliation: Section of Nephrology, The Children's Mercy Hospital and Clinics, University of Missouri at Kansas City, Kansas City, Missouri 64108, USA. tsrivastava@cmh.edu
authors.forename: T
authors.initials: T
authors.lastname: Srivastava
authors.forename: R E
authors.initials: RE
authors.lastname: Garola
authors.forename: H K
authors.initials: HK
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002675:Child, Preschool; D019925:Cyclin A / Q000378:metabolism; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D016193:G1 Phase; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology*; D016196:S Phase
chemical_list: C493964:CDKN1C protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D050760:Cyclin-Dependent Kinase Inhibitor p27