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BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION Downregulation of Muc1 and Muc3A expression by prolonged cold ischemic time may play a potential role in large bile duct injury early after OLT.

BACKGROUND: The pathogenesis of nonanastomotic strictures with a patent hepatic artery remains to be investigated. This study focuses on the role of cholangiocyte bile acid transporters in bile duct injury after liver transplantation. METHODS: Sprague-Dawley rats were divided into three groups (n=20 for each): the sham-operated group (Sham), the transplant group with 1-hr donor liver cold preservation (CP-1h), and the transplant group with 12-hr donor liver cold preservation (CP-12h). Bile was collected for biochemical analysis. The histopathologic evaluation of bile duct injury was performed and the cholangiocyte bile acid transporters apical sodium-dependent bile acid transporter (ASBT), ileal lipid binding protein (ILBP), and Ostalpha/Ostbeta were investigated. RESULTS.: The immunohistochemical assay suggested that ASBT and ILBP were expressed exclusively on large bile duct epithelial cells, whereas Ostalpha and Ostbeta were expressed on both small and large bile ducts. Western blot and quantitative polymerase chain reaction analysis showed that the expression levels of these transporters dramatically decreased after transplantation. It took seven to 14 days for ILBP, Ostalpha, and Ostbeta to recover, whereas ASBT recovered within 3 days and even reached a peak above the normal level seven days after operation. In the CP-12h group, the ratios of the ASBT/ILBP, ASBT/Ostalpha and ASBT/Ostbeta expression levels were correlated with the injury severity scores of large but not small bile ducts. CONCLUSIONS: The results suggest that the unparallel alteration of cholangiocyte bile acid transporters may play a potential role in large bile duct injury after liver transplantation with prolonged donor liver preservation.