title: Donor Graft MicroRNAs: A Newly Identified Player in the Development of New-onset Diabetes After Liver Transplantation.
abstract: New-onset diabetes after liver transplantation (NODALT) is a frequent complication with an unfavorable outcome. We previously demonstrated a crucial link between donor graft genetics and the risk of NODALT. We selected 15 matched pairs of NODALT and non-NODALT liver recipients using propensity score matching analysis. The donor liver tissues were tested for the expression of 10 microRNAs (miRNAs) regulating human hepatic glucose homeostasis. The biological functions of potential target genes were predicted using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Both miR-103 and miR-181a were significantly highly expressed in the NODALT group as compared to the non-NODALT group. The predicted target genes (e.g. Irs2, Pik3r1, Akt2, and Gsk3b) were involved in glucose import and the insulin signaling pathway. We also observed dysregulation of miRNAs (e.g. let-7, miR-26b, miR-145, and miR-183) in cultured human hepatocytes treated with tacrolimus or high glucose, the two independent risk factors of NODALT identified in this cohort. The hepatic miRNA profiles altered by tacrolimus or hyperglycemia were associated with insulin resistance and glucose homeostatic imbalance as revealed by enrichment analysis. The disease susceptibility miRNA expressive pattern could be imported directly from the donor and consolidated by the transplant factors.
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ling
authors.affiliation: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.|Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000328:Adult; D017668:Age of Onset; D003920:Diabetes Mellitus / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D014019:Tissue Donors
chemical_list: D035683:MicroRNAs
keywords: calcineurin inhibitor: tacrolimus; diabetes: new onset/posttransplant; donors and donation: donor evaluation; immunosuppressant; liver allograft function/dysfunction; liver transplantation/hepatology; microarray/gene array; translational research/science