Trps1 Regulates Biliary Epithelial-Mesenchymal Transition and Has Roles during Biliary Fibrosis in Liver Grafts: A Preliminary Study

Abstract

ObjectiveTo investigate the role(s) of Trps1 in non-anastomotic biliary stricture (NABS) following liver transplantation.MethodsImmunohistochemical and histological techniques were used to detect Trps1, E-cadherin, CK19, vimentin, α-SMA, and collagen deposition. Human intrahepatic biliary epithelial cells (HIBECs) were infected with a Trps1 adenovirus, or transfected with Trps1 short-interfering RNAs (siRNAs). Reverse transcription polymerase chain reaction (RT-PCR) assays and western blotting were used to determine expression levels of epithelial and mesenchymal markers, and Trps1 in HIBECs.ResultsExpression of Trps1 and epithelial markers was down-regulated or absent in NABS liver samples. Mesenchymal markers were seen in biliary epithelial cells (BECs), with collagen deposited around the bile duct. Trps1 expression positively correlated with epithelial markers. Expression of epithelial marker mRNAs and proteins in HIBECs decreased with prolonged cold preservation (CP), while mesenchymal marker expression increased. A 12-h CP period led to increased Trps1 mRNA and protein levels. Expression of E-cadherin was increased in HIBECs following Trps1 adenovirus infection and CP/reperfusion injury (CPRI), with vimentin expression levels reduced and CPRI-mediated epithelial-mesenchymal transition (EMT) inhibited. Transfection of HIBECs with Trps1 siRNAs in conjunction with CPRI revealed that E-cadherin expression was decreased, vimentin expression was increased, and CPRI-mediated EMT was promoted.ConclusionTrps1 is involved in NABS pathogenesis following liver transplantation and negatively correlates with BEC EMT and biliary fibrosis in liver grafts. Trps1 demonstrates antagonistic effects that could reverse EMT.

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

“…Western blotting was performed as previously described [15]. Antibodies against E-cadherin, N-cadherin and Vimentin were purchased from Proteintech.…”

Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis

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Evaluation of hepatic vascular endothelial injury during liver storage by molecular detection and targeted contrast‐enhanced ultrasound imaging

“…The progressive endothelitis and endothelial damage may cause biliary damage after retransplantation. Biliary injury is the most catastrophic pathophysiological reason that is the cause for delayed graft failure of the solid organ after transplantation . The results of this study provide strong evidence that prior vascular injury may cause deficient perfusion of biliary ductules after retransplantation, resulting in biliary injury.…”

“…Chief among the post‐procedural complication are the possibilities of delayed graft failure . The commonest non‐immunologic reason for delayed graft failure after liver transplantation is the development of biliary injuries .…”