Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis

Yasuhiko Kimura, Patrick S.C. Leung, Thomas P. Kenny, Judy Van De Water, Mikio Nishioka, Andrew S. Giraud, James Neuberger, Gordon Benson, Rashmi Kaul, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1227-1235
Number of pages9
JournalHepatology
Volume36
Issue number5 II
DOIs
StatePublished - 1 Nov 2002

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Biliary Liver Cirrhosis
Bile Ducts
Epithelial Cells
Liver
Trefoil Factor-3
Intrahepatic Bile Ducts
Gene Expression
Sclerosing Cholangitis
Bile
Hepacivirus
Cell Movement
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Proteins
Immunohistochemistry
Inflammation

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Kimura, Y., Leung, P. S. C., Kenny, T. P., Van De Water, J., Nishioka, M., Giraud, A. S., ... Gershwin, M. E. (2002). Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. Hepatology, 36(5 II), 1227-1235. https://doi.org/10.1053/jhep.2002.36157
Kimura, Yasuhiko ; Leung, Patrick S.C. ; Kenny, Thomas P. ; Van De Water, Judy ; Nishioka, Mikio ; Giraud, Andrew S. ; Neuberger, James ; Benson, Gordon ; Kaul, Rashmi ; Ansari, Aftab A. ; Coppel, Ross L. ; Gershwin, M. Eric. / Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. In: Hepatology. 2002 ; Vol. 36, No. 5 II. pp. 1227-1235.
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abstract = "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.",
author = "Yasuhiko Kimura and Leung, {Patrick S.C.} and Kenny, {Thomas P.} and {Van De Water}, Judy and Mikio Nishioka and Giraud, {Andrew S.} and James Neuberger and Gordon Benson and Rashmi Kaul and Ansari, {Aftab A.} and Coppel, {Ross L.} and Gershwin, {M. Eric}",
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Kimura, Y, Leung, PSC, Kenny, TP, Van De Water, J, Nishioka, M, Giraud, AS, Neuberger, J, Benson, G, Kaul, R, Ansari, AA, Coppel, RL & Gershwin, ME 2002, 'Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis', Hepatology, vol. 36, no. 5 II, pp. 1227-1235. https://doi.org/10.1053/jhep.2002.36157

Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. / Kimura, Yasuhiko; Leung, Patrick S.C.; Kenny, Thomas P.; Van De Water, Judy; Nishioka, Mikio; Giraud, Andrew S.; Neuberger, James; Benson, Gordon; Kaul, Rashmi; Ansari, Aftab A.; Coppel, Ross L.; Gershwin, M. Eric.

In: Hepatology, Vol. 36, No. 5 II, 01.11.2002, p. 1227-1235.

Research output: Contribution to journalArticle

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.

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Kimura Y, Leung PSC, Kenny TP, Van De Water J, Nishioka M, Giraud AS et al. Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. Hepatology. 2002 Nov 1;36(5 II):1227-1235. https://doi.org/10.1053/jhep.2002.36157