Korean J Nephrol.  2005 May;24(3):366-374.

Apoptosis in Autosomal Dominant Polycystic Kidney Disease

Affiliations
  • 1Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. kyubeck.lee@samsung.com
  • 2Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 3Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.

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.

Keyword

Autosomal dominant polycystic kidney disease; Apoptosis; Transforming growth factor beta; Smad 2/3; Bcl-2 protein

MeSH Terms

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
Transforming Growth Factor beta
Transforming Growth Factor beta1
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