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Apoptosis occurs differentially according to glomerular size in diabetic kidney disease

 Dong-Sub Jung  ;  Sun Ha Lee  ;  Seung-Jae Kwak  ;  Jin Ji Li  ;  Do Hee Kim  ;  Bo-Young Nam  ;  Hye Young Kang  ;  Tae Ik Chang  ;  Jung Tak Park  ;  Seung Hyeok Han  ;  Tae-Hyun Yoo  ;  Shin-Wook Kang 
 Nephrology Dialysis Transplantation, Vol.27(1) : 259-266, 2012 
Journal Title
 Nephrology Dialysis Transplantation 
Issue Date
BACKGROUND: Apoptosis; which is involved in the process of mesangial cell and podocyte loss in diabetic nephropathy; is known to be regulated by protein kinase B/Akt (Akt). A number of studies have therefore investigated the activity of Akt under diabetic conditions; but the results have not been consistent. In this study; we hypothesized that apoptosis may occur differentially and that Akt may be differentially activated according to glomerular size in diabetic kidney disease. METHODS: Fifty male Sprague-Dawley rats were injected intraperitoneally with diluent (C; n = 25) or streptozotocin (DM; n = 25). After 3 months; glomeruli were isolated using sieves with pore sizes of 250; 150; 125 and 75 μm and then classified into large glomeruli (on the 125-μm sieve; LG) and small glomeruli (on the 75-μm sieve; SG) groups. Western blot analyses for phospho-Akt; apoptosis-related molecules (Bax; Bcl-2; active fragments of Caspase-3 and phospho-p53) and cyclin-dependent kinase inhibitors were performed. CONCLUSIONS: The numbers of total cells and podocytes in isolated glomeruli were determined using transmission electron microscopy. Akt phosphorylation was significantly decreased in DM-LG; while it was significantly increased in DM-SG (P < 0.05). The ratio of Bax/Bcl-2 protein expression and active fragments of Caspase-3 and phospho-p53 protein expression were significantly increased in DM-LG compared to DM-SG and C-SG (P < 0.001 and P < 0.01; respectively). In contrast; the expression of p27(Kip1) and p21(Cip1) was significantly increased in DM-SG compared to DM-LG and C-SG (P < 0.05). The numbers of total glomerular cells and podocytes were significantly decreased in DM-LG (P < 0.05). In conclusion; these data show differential expression of Akt activity and apoptosis-related molecules according to glomerular size in diabetic nephropathy; suggesting that apoptosis may be more operative in more hypertrophic glomeruli; resulting in fewer glomerular cells and podocytes in diabetic nephropathy.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
강혜영(Kang, Hye Young)
곽승재(Kwak, Seung Jae)
남보영(Nam, Bo Young)
박정탁(Park, Jung Tak) ORCID logo https://orcid.org/0000-0002-2325-8982
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
이순하(Lee, Sun Ha)
장태익(Chang, Tae Ik)
정동섭(Jung, Dong Sub)
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
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