Mitotic cell cycle proteins increase in podocytes despite lack of proliferation.
BACKGROUND
Podocyte proliferation is an uncommon response to glomerular injury and its lack may underlie the development of glomerulosclerosis. However, whether podocytes have the capacity to enter and finish mitosis and cytokinesis is not known.


METHODS
The expression of mitotic cell cycle proteins (phosphorylated Histone 3, Cdc2, cyclin B1 and B2) was examined by immunohistochemistry in kidneys of embryonal mice, transgenic HIV-mice, and rats with experimental membranous nephropathy (passive Heymann nephritis, PHN). Mitotic proteins also were measured by Western blot in glomerular protein from PHN-rats and the activity of mitotic cyclins was quantified by histone kinase assay.


RESULTS
Mitotic proteins were increased in embryonal mouse glomeruli during the S- and comma-shaped stages and were absent at the capillary loop stage and in mature rodent glomeruli. There was an increase in podocyte expression of Cdc2, cyclin B1 and B2 and phosphorylated histone 3 in PHN rats, and in HIV transgenic mice.


CONCLUSIONS
Podocytes have the ability to increase cell cycle proteins required for mitosis. Without obvious differences in the expression of the major mitotic proteins in PHN- and HIV-nephropathy, a regulatory disturbance in cytokinesis might be responsible for the development of polynucleated cells and a lack of podocyte proliferation in experimental glomerular disease.
Petermann
Arndt T
AT
Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Pippin
Jeffrey
J
Hiromura
Keiju
K
Monkawa
Toshi
T
Durvasula
Raghu
R
Couser
William G
WG
Kopp
Jeffrey
J
Shankland
Stuart J
SJ
D016263:AIDS-Associated Nephropathy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002455:Cell Division; D019926:Cyclin B / Q000378:metabolism; D005921:Glomerulonephritis / Q000473:pathology*; D006678:HIV / Q000235:genetics; D007678:Kidney Glomerulus / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019926:Cyclin B; D016203:CDC2 Protein Kinase