title: Plasma microRNA, a potential biomarker for acute rejection after liver transplantation.
abstract: BACKGROUND
  Acute rejection (AR) of an organ transplant is a life-threatening complication. Currently, there are few diagnostic biomarkers suitable for clinical application. We aim to determine the potential of plasma microRNAs as biomarkers for AR.
  
  
  METHODS
  Using rat orthotopic liver transplantation model and microarrays, we compared the difference in the spectrum and levels of microRNAs in both plasma and grafts between AR rats and control. AR-related plasma microRNAs were selected and validated using real-time quantification polymerase chain reaction. Plasma from AR rats with or without tacrolimus treatment was used for microRNA dynamic monitoring. To clarify the origin of AR-related plasma microRNAs, drug-induced liver damage rat model were performed and in situ hybridization was used to detect and localize the specific microRNA in allografts.
  
  
  RESULTS
  We found that plasma miR-122, miR-192, and miR-146a was significantly up-regulated when AR occur (fold change>2; P<0.05) and the elevation could be repressed by immunosuppression. In liver injury rat model, up-regulated plasma miR-122 (fold change=22.126; P=0.002) and miR-192 (fold change=8.833; P<0.001) rather than miR-146a (fold change=1.181; P=0.594) were observed. Further study demonstrated that miR-146a was up-regulated by sixfold in microvesicles isolated from AR plasma, whereas miR-122 and miR-192 showed no distinct change. In situ hybridization revealed that the portal areas of the AR graft were brimming with lymphocytes, which showed highly intense staining for miR-146a.
  
  
  CONCLUSIONS
  Our study provides the global fingerprint of plasma microRNAs in AR rats and suggests that plasma miR-122 and miR-192 reflect liver injury, whereas miR-146a may associate with cellular rejection.
authors: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), the Chinese Ministry of Education, and Shanghai Key Laboratory for Organ Transplantation, Shanghai, PR China.
authors: Jie
authors: J
authors: Hu
authors: Zheng
authors: Z
authors: Wang
authors: Chang-Jun
authors: CJ
authors: Tan
authors: Bo-Yi
authors: BY
authors: Liao
authors: Xin
authors: X
authors: Zhang
authors: Min
authors: M
authors: Xu
authors: Zhi
authors: Z
authors: Dai
authors: Shuang-Jian
authors: SJ
authors: Qiu
authors: Xiao-Wu
authors: XW
authors: Huang
authors: Jian
authors: J
authors: Sun
authors: Qi-Man
authors: QM
authors: Sun
authors: Yi-Feng
authors: YF
authors: He
authors: Kang
authors: K
authors: Song
authors: Qi
authors: Q
authors: Pan
authors: Ying
authors: Y
authors: Wu
authors: Jia
authors: J
authors: Fan
authors: Jian
authors: J
authors: Zhou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; C580643:MIRN122 microRNA, rat; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs