Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats |
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Authors: | Svegliati-Baroni Gianluca Ghiselli Roberto Marzioni Marco Alvaro Domenico Mocchegiani Federico Saccomanno Stefania Sisti Valerio Ugili Laura Orlando Fiorenza Alpini Gianfranco Saba Vittorio Benedetti Antonio |
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Affiliation: | Clinica di Gastroenterologia, Università Politecnica delle Marche, INRCA, IRCCS, Via Tronto, Ancona, 60020, Italy. g.svegliati@univpm.it |
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Abstract: | 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 17beta-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, 17beta-estradiol significantly reduced cholangiocyte apoptosis. 17beta-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 17beta-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, 17beta-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. |
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Keywords: | Cholangiocyte Proliferation Cholestasis |
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