Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Expression of Anion Exchanger and CFTR in the Hepatocyte and Cholangiocytes in Bile Duct-Ligated Rat

담관 결찰 쥐의 간세포와 담관세포의 anion exchanger와 CFTR 발현

  • Lee, Jae-Dong (Department of Gastroenterology/Hepatology, College of Medicine, Konkuk University) ;
  • Wang, Joon-Ho (Department of Gastroenterology/Hepatology, College of Medicine, Konkuk University) ;
  • Ki, Seung-Seog (Department of Gastroenterology/Hepatology, College of Medicine, Konkuk University) ;
  • Choe, Won-Hyeok (Department of Gastroenterology/Hepatology, College of Medicine, Konkuk University) ;
  • Park, Jae-Seung (Department of Medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine) ;
  • Cho, Won-Kyoo (Department of Medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine) ;
  • Park, Jung-Jun (Division of Sport Science, Pusan National University) ;
  • Kim, Hong-Su (Department of Gastroenterology/Hepatology, College of Medicine, Soonchunhyang University)
  • 이재동 (건국대학교 의과대학 내과학교실) ;
  • 왕준호 (건국대학교 의과대학 내과학교실) ;
  • 기승석 (건국대학교 의과대학 내과학교실) ;
  • 최원혁 (건국대학교 의과대학 내과학교실) ;
  • 박재승 (미국 인디아나 의과대학 소화기내과) ;
  • 조원규 (미국 인디아나 의과대학 소화기내과) ;
  • 박정준 (부산대학교 스포츠과학부) ;
  • 김홍수 (순천향대학교 의과대학 내과학교실)
  • Received : 2011.11.14
  • Accepted : 2011.12.14
  • Published : 2011.12.31
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Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.

본 연구는 흰쥐의 담관 세포와 간세포에서 CFTR과 $AE1{\cdot}AE2{\cdot}AE3$ 유전자들의 발현 유무를 조사하고 흰쥐에서 담관 결찰 후 AE2 유전자의 발현의 변화를 관찰하고자 하였다. 200-250 g의 Sprague Dawley 계 흰쥐 24마리의 총담관을 결찰한 후 4 주 동안 1 주일에 6마리씩 희생하여 간세포와 담관 세포를 분리하였다. 6마리는 대조군으로 사용하여 간세포와 담관 세포에서 CFTR 유전자와 $AE1{\cdot}AE2$와 AE3 유전자 발현을 조사하고 담관 결찰 후 1 2 3 4주 간격으로 AE2 유전자 발현을 조사하였다. $AE1{\cdot}AE2$ 와 AE3는 간세포와 담관 세포에서 발현되었고 CFTR은 담관 세포에서만 발현되었다. 담관 결찰 담관세포군에서 AE2 유전자의 발현은 대조군인 정상 담관세포군에 비해서 낮았다. 결찰 담관세포군에서 AE2 유전자의 발현은 결찰 기간에 따라 차이가 없었다. 담관 결찰 간세포군에서 AE2 유전자의 발현은 대조군인 정상 간세포군에 비해서 경계적 유의성을 보이며 증가하는 경향이 있었다. 결찰 간세포군에서 AE2 유전자의 발현은 결찰 기간에 따라 차이는 없었다. 따라서 $CFTR{\cdot}AE1{\cdot}AE2$ 그리고AE3 는 간세포와 담관 세포에서 중탄산염이온과 수액을 매개하는 주된 이온 전달체라는 사실을 고려할 때 담도 담즙정체 간질환에서CFTR과 AE2 발현의 변화는 병리학적 기전에 중요한 역할을 할 수 있으리라고 생각된다.

Keywords

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