title: Apoptotic cell loss following cell proliferation in renal glomeruli of Otsuka Long-Evans Tokushima Fatty rats, a model of human type 2 diabetes.
abstract: BACKGROUND
  The mechanism of glomerular cell loss during the late stage of diabetic nephropathy is unknown.
  
  
  METHODS
  We examined cell population, proliferation, apoptosis, and immunohistochemical expression of apoptosis-related proteins, Bcl-2 and Bax, in renal glomeruli of the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of human type 2 diabetes. 10-, 30-, 50-, and 70-week-old rats were used (n = 5-8). Control was the Long-Evans Tokushima Otsuka (LETO) rat.
  
  
  RESULTS
  The cell population in renal glomeruli of OLETF rats progressively increased with age, but decreased at 70 weeks old. High cell proliferative activity based on proliferating cell nuclear antigen (PCNA) expression was limited during the early stage, whereas by in situ nick end-labeling (TUNEL), Taq polymerase based in situ ligation, and electron microscopy, apoptosis was detected during the late stage (50 and 70 weeks old). Augmented expression of Bax, but not of Bcl-2, was evident in glomeruli of OLETF rats during the late stage, which contributed to an increased Bax/Bcl-2 ratio.
  
  
  CONCLUSIONS
  It appears that high cell proliferative activity and the subsequent cell loss via apoptosis counterbalance each other and determine glomerular cell population of OLETF rats. Augmented Bax expression may be one of the important regulators of this apoptosis.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Ichijiro
authors.initials: I
authors.lastname: Murata
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Asano
authors.forename: Hirotake
authors.initials: H
authors.lastname: Sano
authors.forename: Koh
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Kagawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Baba
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D051381:Rats; D020334:Rats, Inbred OLETF; D014157:Transcription Factors / Q000032:analysis; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein