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11 December 2017 : Laboratory Research  

MicroRNA-146b-5p Identified in Porcine Liver Donation Model is Associated with Early Allograft Dysfunction in Human Liver Transplantation

Cheukfai Li123ABCDEF, Qiang Zhao123ABCDE, Wei Zhang123BCE, Maogen Chen123BCD, Weiqiang Ju123BCD, Linwei Wu123BCD, Ming Han123BDF, Yi Ma12BDEF, Xiaofeng Zhu123ABG, Dongping Wang123ABCDEFG*, Zhiyong Guo123ABCDEFG, Xiaoshun He123ABCDEFG

DOI: 10.12659/MSM.907542

Med Sci Monit 2017; 23:5876-5884

Abstract

BACKGROUND: Poor transplant outcome was observed in donation after brain death followed by circulatory death (DBCD), since the donor organs suffered both cytokine storm of brain death and warm ischemia injury. MicroRNAs (miRNAs) have emerged as promising disease biomarkers, so we sought to establish a miRNA signature of porcine DBCD and verify the findings in human liver transplantation.

MATERIAL AND METHODS: MiRNA expression was determined with miRNA sequencing in 3 types of the porcine model of organ donation, including donation after brain death (DBD) group, donation after circulatory death (DCD) group, and DBCD group. Bioinformatics analysis was performed to reveal the potential regulatory behavior of target miRNA. Human liver graft biopsy samples after reperfusion detected by fluorescence in situ hybridization were used to verify the expression of target miRNA.

RESULTS: We compared miRNA expression profiles of the 3 donation types. The porcine liver graft miR-146b was significantly increased and selected in the DBCD group versus in the DBD and DCD groups. The donor liver expression of human miR-146b-5p, which is homologous to porcine miR-146b, was further examined in 42 cases of human liver transplantations. High expression of miR-146b-5p successfully predicted the post-transplant early allograft dysfunction (EAD) with the area under the ROC curve (AUC) 0.759 (P=0.004).

CONCLUSIONS: Our results revealed the miRNA signature of DBCD liver grafts for the first time. The miR-146b-5p may have important clinical implications for monitoring liver graft function and predicating transplant outcomes.

Keywords: Biological Markers, Liver Transplantation, Tissue and Organ Procurement

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750