title: Transcriptional Perturbations in Graft Rejection.
abstract: BACKGROUND
  Understanding the regulatory interplay of relevant microRNAs (miRNAs) and messenger RNAs (mRNAs) in the rejecting allograft will result in a better understanding of the molecular pathophysiology of alloimmune injury.
  
  
  METHODS
  One hundred sixty-seven allograft biopsies, with (n = 47) and without (n = 120) central histology for Banff scored acute rejection (AR), were transcriptionally profiled for mRNA and miRNA by whole genome microarrays and multiplexed microfluidic quantitative polymerase chain reaction, respectively. A customized database was curated (GO-Elite) and used to identify AR-specific dysregulated mRNAs and the role of perturbations of their relevant miRNAs targets during AR.
  
  
  RESULTS
  The AR-specific changes in 1035 specific mRNAs were mirrored by AR-specific perturbations in 9 relevant miRNAs as predicted by Go-Elite and were regulated specifically by p53 and forkhead box P3. Infiltrating lymphocytes and the renal tubules drove the miRNA tissue pertubations in rejection, involving message degradation and transcriptional/translational activation. The expression of many of these miRNAs significantly associated with the intensity of the Banff-scored interstitial inflammation and tubulitis.
  
  
  CONCLUSIONS
  There is a highly regulated interplay between specific mRNA/miRNAs in allograft rejection that drive both immune-mediated injury and tissue repair during AR.
authors.affiliation: 1 Department of Surgery, Stanford University, Stanford, CA. 2 Department of Surgery, University of California San Francisco, San Francisco, CA. 3 Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Vitalone
authors.forename: Tara K
authors.initials: TK
authors.lastname: Sigdel
authors.forename: Nathan
authors.initials: N
authors.lastname: Salomonis
authors.forename: Reuben D
authors.initials: RD
authors.lastname: Sarwal
authors.forename: Szu-Chuan
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D030541:Databases, Genetic; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry* / Q000276:immunology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger