상염색체 우성 다낭신에서 세포자멸사에 대한 연구 = Apoptosis in Autosomal Dominant Polycystic Kidney Disease

다국어 초록 (Multilingual 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-β1 (TGF-β1)-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-β1, 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 (×400) 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-β1 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-β1-Smad2/3 signal pathway and decreased anti-apoptotic Bcl-2 protein seem to be involved in apoptotic pathway of ADPKD. (Korean J Nephrol 2005;24(3):366-374)

국문 초록 (Abstract)

목 적:상염색체 우성 다낭신에서 세포자멸사는 주된 조직병리학적 소견의 하나로 이 환자군에서 낭종 형성 및 신기능의 지속적 감소에 관여한다고 여겨지나 그 기전은 명확하지 않다. 이에 저자들은 상염색체 우성 다낭신 환자의 신장 조직에서 세포자멸사 정도와 다양한 기능을 하는 사이토카인으로 세포자멸사에도 관여하는 것으로 알려진 transforming growth factor (TGF)-β1과 그 신호중간물인 Smad2/3, 세포자멸사 억제인자인 Bcl-2 단백질의 발현을 면역조직화학 염색을 통해 알아보고자 하였다.
방 법:말기신부전에 이르러 신이식을 시행하는 상염색체 우성 다낭신 환자 (n=4)의 신장 조직을 얻어 TdT-mediated dUTP nick end labeling (TUNEL) 방법으로 세포자멸사 정도를 판정하고, TGF-β1, Smad2/3, Bcl-2 단백질에 대한 면역조직화학 염색을 시행하여 정상군(n=4)과 비교하였다.
결 과:세뇨관 세포의 세포자멸사는 정상군 (0.36±0.10%)에서는 거의 관찰되지 않았으며, 상염색체 우성 다낭신군 (9.01±1.85%)에서 유의하게 증가되었다 (p=0.020). 상염색체 우성 다낭신군에서의 세포자멸사는 낭종에 배열한 상피세포에서 뿐만 아니라, 비낭종성 세뇨관에서도 관찰되었으며, 일부 간질조직에서도 관찰되었으나, 사구체에서는 거의 관찰되지 않았다. 면역조직화학적 염색으로 상염색체 우성 다낭신군에서는 정상군에서 보다 낭종성 및 비낭종성 세뇨관 상피세포에서 TGF-β1, Smad2/3 단백질의 과발현이 관찰되었으며, Bcl-2 단백질의 발현은 감소되었다.
결 론:상염체 우성 다낭신의 병인이나 진행과정에 세포자멸사가 관여하며, 여기에는 활성화된 TGF-β1-Smad2/3 신호체계와 감소된 Bcl-2가 관여하는 것으로 보인다.

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