Downregulation of Mucins in Graft Bile Ducts After Liver Transplantation in Rats

Abstract

Nonanastomotic biliary strictures represent a serious complication after orthotopic liver transplantation (OLT). This study investigates the potential role of mucins in bile duct injury after OLT. Sprague-Dawley rats were divided into four groups: normal group (Normal, n=5), sham-operated group (Sham, n=20), OLT group with 1 hr donor cold ischemic time (n=20), and OLT group with 12 hr donor cold ischemic time (OLTn=20). Expression of mucins and GATA factors in bile ducts was examined by real-time polymerase chain reaction, immunohistochemistry, and immunoblotting. Bile was collected for biochemical analysis, and the histological changes associated with bile duct injury were evaluated. In normal bile ducts, Muc1, Muc2, Muc3A, Muc4, and Muc6 mRNA were expressed, whereas Muc5AC mRNA was undetectable. The expression of Muc1, Muc3A, and Muc4 but not Muc2 and Muc6 at mRNA level in graft bile ducts decreased remarkably early after OLT. The decreased expression of Muc1 and Muc4 was further confirmed at protein level by immunohistochemistry and immunoblotting. Downregulation of Muc1 and Muc3A expression by prolonged cold ischemic time was significantly associated with the injury severity scores of large but not small bile ducts. Among six GATA factors, GATA3, GATA4, and GATA6 mRNA were expressed in normal bile ducts. GATA4 and GATA6 mRNA levels decreased significantly after OLT. Downregulation of Muc1 and Muc3A expression by prolonged cold ischemic time may play a potential role in large bile duct injury early after OLT.