TY - JOUR
T1 - Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis
AU - Kimura, Yasuhiko
AU - Leung, Patrick S.C.
AU - Kenny, Thomas P.
AU - Van De Water, Judy
AU - Nishioka, Mikio
AU - Giraud, Andrew S.
AU - Neuberger, James
AU - Benson, Gordon
AU - Kaul, Rashmi
AU - Ansari, Aftab A.
AU - Coppel, Ross L.
AU - Gershwin, M. Eric
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Intestinal trefoil factor (ITF) promotes epithelial cell migration and mucosal restitution during inflammation. We used real-time quantitative PCR, in situ nudeic acid hybridization, and immunohistochemistry to study the expression of the ITF gene and protein expression in the liver of primary biliary cirrhosis (PBC) and controls. There were significantly higher levels of ITF messenger RNA (mRNA) in PBC liver compared with primary sclerosing cholangitis (PSC) (P < .05) or normal controls (P < .001) and also higher in hepatitis C virus (HCV) liver (P < .05) and cryptogenic cirrhosis (P < .01) compared with normal controls. However, only in PBC was there a significant difference between small (interlobular and bile ductules) and large (intrahepatic and septal) bile ducts. Using in situ hybridization, the highest levels of ITF gene expression were localized to the large bile ducts in PBC. This differential expression of ITF was also noted at the protein level. Thus, in PBC, although 92% of large bile ducts expressed the ITF protein, only 2% of small bile ducts (P < .0001) expressed ITF. In contrast, in control livers, 34% of large bile ducts and 13% of small bile ducts expressed ITF. ITF protein is absent in small bile ducts in all stages of PBC. In conclusion, the expression of ITF may play an important role in bile duct damage. In small bile ducts, ITF production in response to damage is absent, making such cells vulnerable to damage and providing a thesis for the selective loss of small, but not large, bile ducts in PBC.
AB - Intestinal trefoil factor (ITF) promotes epithelial cell migration and mucosal restitution during inflammation. We used real-time quantitative PCR, in situ nudeic acid hybridization, and immunohistochemistry to study the expression of the ITF gene and protein expression in the liver of primary biliary cirrhosis (PBC) and controls. There were significantly higher levels of ITF messenger RNA (mRNA) in PBC liver compared with primary sclerosing cholangitis (PSC) (P < .05) or normal controls (P < .001) and also higher in hepatitis C virus (HCV) liver (P < .05) and cryptogenic cirrhosis (P < .01) compared with normal controls. However, only in PBC was there a significant difference between small (interlobular and bile ductules) and large (intrahepatic and septal) bile ducts. Using in situ hybridization, the highest levels of ITF gene expression were localized to the large bile ducts in PBC. This differential expression of ITF was also noted at the protein level. Thus, in PBC, although 92% of large bile ducts expressed the ITF protein, only 2% of small bile ducts (P < .0001) expressed ITF. In contrast, in control livers, 34% of large bile ducts and 13% of small bile ducts expressed ITF. ITF protein is absent in small bile ducts in all stages of PBC. In conclusion, the expression of ITF may play an important role in bile duct damage. In small bile ducts, ITF production in response to damage is absent, making such cells vulnerable to damage and providing a thesis for the selective loss of small, but not large, bile ducts in PBC.
UR - http://www.scopus.com/inward/record.url?scp=0036829952&partnerID=8YFLogxK
U2 - 10.1053/jhep.2002.36157
DO - 10.1053/jhep.2002.36157
M3 - Article
C2 - 12395334
AN - SCOPUS:0036829952
SN - 0270-9139
VL - 36
SP - 1227
EP - 1235
JO - Hepatology
JF - Hepatology
IS - 5
ER -
