Apoptosis in Autosomal Dominant Polycystic Kidney Disease.
- Author:
Hyun Young LHEE
1
;
Kyu Beck LEE
;
Hyang KIM
;
Seoung Wan CHAE
;
Moon Hyang PARK
Author Information
1. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. kyubeck.lee@samsung.com
- Publication Type:Original Article
- Keywords:
Autosomal dominant polycystic kidney disease;
Apoptosis;
Transforming growth factor beta;
Smad 2/3;
Bcl-2 protein
- MeSH:
Apoptosis*;
DNA Fragmentation;
Epithelial Cells;
Humans;
Immunohistochemistry;
Kidney;
Kidney Failure, Chronic;
Kidney Transplantation;
Polycystic Kidney Diseases;
Polycystic Kidney, Autosomal Dominant*;
Signal Transduction;
Transforming Growth Factor beta;
Transforming Growth Factor beta1;
Up-Regulation
- From:Korean Journal of Nephrology
2005;24(3):366-374
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Apoptosis is one of the major histopathologic features of autosomal dominant polycystic kidney disease (ADPKD) and may be causally related to the cystogenesis and the progressive deterioration of the renal function in this population. The purpose of this study is to determine whether transforming growth factor-beta1 (TGF-beta1)-Smad2/3 signal pathway, antiapoptotic Bcl-2 proteins are involved in apoptotic pathway in the pathogenesis of ADPKD. METHODS: Human polycystic kidneys were collected from four ADPKD patients with end stage renal disease who were taken renal transplantation. We evaluated TdT-mediated dUTP nick end labeling (TUNEL) assay to detect apoptotic DNA fragmentation in polycystic kidneys compared to normal kidneys. Expression of TGF-beta1, Smad2/3 and Bcl-2 proteins was also detected by immunohistochemistry. RESULTS: The number of apoptotic nuclei in polycystic kidneys was markedly increased, as compared with normal kidneys. Apoptotic cells in tubules expressed as a percentage of total tubular cells within 10 random high power fields (x400) were significantly increased in ADPKD group than in normal group (9.01+/-1.85%, 0.36+/-0.10%, p=0.020). Apoptotic nuclei were detected not only in cells lining the expanded cystic wall but also in the noncystic tubular epithelial cells. Apoptotic nuclei were also demonstrated in the interstitium occasionally but rarely observed in the glomeruli. Immunohistochemical findings of polycystic kidneys showed increased expression of TGF-beta1 proteins and Smad2/3 proteins, and decreased expression of Bcl-2 proteins in cystic and noncystic tubular epitheial cells as opposed to other parts of the kidney, as compared with normal kidneys. CONCLUSION: Upregulation of TGF-beta1-Smad2/3 signal pathway and decreased anti-apoptotic Bcl-2 protein seem to be involved in apoptotic pathway of ADPKD.
