Interleukin-33 / Cyclin D1 imbalance in severe liver steatosis predicts susceptibility to ischemia reperfusion injury Article

Full Text via DOI: 10.1371/journal.pone.0216242 PMID: 31034519 Web of Science: 000466131200047
Open Access International Collaboration

Cited authors

  • Nunez, Kelley G.; Frank, Anderson; Gonzalez-Rosario, Janet; Galliano, Gretchen; Bridle, Kim; Crawford, Darrell; Seal, John; Abbruscato, Frank; Vashistha, Himanshu; Thevenot, Paul T.; Cohen, Ari J.


  • Transplanting donor livers with severe macrosteatosis is associated with increased risk of primary non-function (PNF). The purpose of this study was to identify steatosis-driven biomarkers as a predisposition to severe liver damage and delayed recovery following ischemia reperfusion injury. Wistar rats were fed a methionine-and choline-deficient (MCD) diet for up to three weeks to achieve severe macrosteatosis (>90%). Animals underwent diet withdrawal to control chow and/or underwent ischemia reperfusion and partial hepatectomy injury (I/R-PHx) and reperfused out to 7 days on control chow. For animals with severe macrosteatosis, hepatic levels of IL-33 decreased while Cyclin D1 levels increased in the absence of NF-kappa B p65 phosphorylation. Animals with high levels of nuclear Cyclin D1 prior to I/R-PHx either did not survive or had persistent macrosteatosis after 7 days on control chow. Survival 7 days after I/R-PHx fell to 57% which correlated with increased Cyclin D1 and decreased liver IL-33 levels. In the absence of I/R-PHx, withdrawing the MCD diet normalized IL-33, Cyclin D1 levels, and I/R-PHx survival back to baseline. In transplanted grafts with macrosteatosis, higher Cyclin D1 mRNA expression was observed. Shifts in Cyclin D1 and IL-33 expression may identify severely macrosteatotic livers with increased failure risk if subjected to I/R injury. Clinical validation of the panel in donor grafts with macrosteatosis revealed increased Cyclin D1 expression corresponding to delayed graft function. This pre-surgical biomarker panel may identify the subset of livers with increased susceptibility to PNF.

Publication date

  • 2019

Published in

International Standard Serial Number (ISSN)

  • 1932-6203


  • 14


  • 4