title: Regulation of molecular pathways in ischemia-reperfusion injury after liver transplantation.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) injury is a multifactorial phenomenon that occurs during the transplant event and frequently compromises early graft function after liver transplantation (LT). Current comprehension of molecular mechanisms and regulation processes of I/R injury lacks clarity. MicroRNA (miRNA) regulation results critical in several biological processes.
  
  
  METHODS
  This study evaluated gene expression and miRNA expression profiles using microarrays in 34 graft biopsies collected at preimplantation (L1) and at 90 min postreperfusion (L2) from consecutives deceased-donor LT recipients. miRNA profiles were first analyzed. Data integration analysis (gene expression/miRNA expression) aimed to identify potential target genes for each identified miRNA from the L1/L2 differential gene expression profile.
  
  
  RESULTS
  Pairwise comparison analyses identified 40 miRNAs and 3168 significantly differentially expressed genes at postreperfusion time compared with preimplantation time. Pathway analysis of miRNAs associated these profiles with antiapoptosis, inhibition of cellular proliferation, and proinflammatory processes. Target analysis identified an miRNA-associated molecular profile of 2172 genes involved in cellular growth and proliferation modulation by cell cycle regulation, cell death and survival, and proinflammatory and anti-inflammatory processes. miRNA-independent genes involved proinflammatory molecules.
  
  
  CONCLUSIONS
  We identified a miRNA profile involved in posttranscriptional regulatory mechanisms in I/R injury post-LT. A better understanding of these molecular processes involved in I/R may contribute to develop new strategies to minimize graft injury.
authors.affiliation: 1 Transplant Division, Department of Surgery, University of Virginia, Charlottesville, VA. 2 Department of Pathology, Virginia Commonwealth University, Richmond, VA. 3 Address correspondence to Daniel G. Maluf, M.D., Liver Transplant Program, Transplant Division, Department of Surgery, University of Virginia, 1300 Jefferson Park Avenue, Barringer 5, Room 5417, Charlottesville, VA.
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Gehrau
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Mas
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Dumur
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Ladie
authors.forename: Jihee L
authors.initials: JL
authors.lastname: Suh
authors.forename: Samuel
authors.initials: S
authors.lastname: Luebbert
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Maluf
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D011184:Postoperative Period; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D035683:MicroRNAs