TY - JOUR
T1 - Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats
AU - Svegliati-Baroni, Gianluca
AU - Ghiselli, Roberto
AU - Marzioni, Marco
AU - Alvaro, Domenico
AU - Mocchegiani, Federico
AU - Saccomanno, Stefania
AU - Sisti, Valerio
AU - Ugili, Laura
AU - Orlando, Fiorenza
AU - Alpini, Gianfranco
AU - Saba, Vittorio
AU - Benedetti, Antonio
PY - 2006/6
Y1 - 2006/6
N2 - Background/Aims: Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats. Methods: After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17β-estradiol or a control solution. Results: Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17β-estradiol significantly reduced cholangiocyte apoptosis. 17β-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17β-estradiol. Conclusions: This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17β-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.
AB - Background/Aims: Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats. Methods: After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17β-estradiol or a control solution. Results: Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17β-estradiol significantly reduced cholangiocyte apoptosis. 17β-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17β-estradiol. Conclusions: This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17β-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.
KW - Cholangiocyte
KW - Cholestasis
KW - Proliferation
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U2 - 10.1016/j.jhep.2005.10.032
DO - 10.1016/j.jhep.2005.10.032
M3 - Article
C2 - 16481066
AN - SCOPUS:33646156160
VL - 44
SP - 1158
EP - 1166
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -