Induction of biliary epithelial wound healing and angiogenesis through IL6 in donor bile ducts after liver transplantation

Background:

Impaired epithelial cell proliferation and angiogenesis after ischemia/reperfusion injury may compromise wound healing of the donor bile duct and may lead to later biliary complications. It is known that IL6 can induce VEGFA and biliary epithelial cell proliferation. The aim of this study was to examine IL6 and VEGFA mRNA expression in the common bile duct at the time of organ retrieval, after cold storage, and during transplantation.

Methods:

Common bile duct samples during donor hepatectomy, after cold storage, and after reperfusion were compared by novel RNAscope in-situ hybridization (ISH) for IL6 and VEGFA mRNA expression. Additional immunohistochemistry for CD45 was done, followed by whole-slide scanning and automated digital image analysis. ISH signal and CD45+ cells were quantified and expressed as spot-area µm2/1000µm2 and cells/1000µm2, respectively.

Results:

Donor hepatectomy bile ducts (n = 5) showed a baseline IL6 (0.3 ± 0.2) and VEGFA (0.6 ± 0.4) mRNA expression that was comparable to the expression levels detected following cold storage for both IL6 (0.5 ± 0.1) and VEGFA (0.8 ± 0.4). However, after reperfusion (n = 5), IL6 expression was markedly increased (1.2 ± 0.2, p =.007) and VEGFA expression levels were also elevated (1.5 ± 2.0). A co-localization of IL6 and VEGFA was observed in epithelial cells during cold storage and in the sub epithelial region after reperfusion. CD45+ cell count decreased from donor hepatectomy (2.5 ± 1.4) to reperfusion (1.3 ± 1.0).

Conclusions:

Increased expression of IL6 and VEGFA mRNA in the common bile duct after reperfusion may facilitate wound healing. Impaired expression of IL6 and VEGFA may have a deleterious effect on wound healing and mitigating preservation injury in donor livers via the IL6 pathway should be considered.