Apoptotic cell loss following cell proliferation in renal glomeruli of Otsuka Long-Evans Tokushima Fatty rats, a model of human type 2 diabetes.
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.
Murata
Ichijiro
I
Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Takemura
Genzou
G
Asano
Kiyoji
K
Sano
Hirotake
H
Fujisawa
Koh
K
Kagawa
Tomoyo
T
Baba
Kaoru
K
Maruyama
Rumi
R
Minatoguchi
Shinya
S
Fujiwara
Takako
T
Fujiwara
Hisayoshi
H
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
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