title: Identification of Circulating miRNAs in a Mouse Model of Nerve Allograft Transplantation under FK506 Immunosuppression by Illumina Small RNA Deep Sequencing.
abstract: BACKGROUND
  This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation in the presence and absence of FK506 immunosuppression.
  
  
  METHODS
  A 1 cm BALB/c donor sciatic nerve graft was transplanted into the sciatic nerve gaps created in recipient C57BL/6 mice with or without daily FK506 immunosuppression [1 mg/(kg·d)]. At 3, 7, and 14 d after nerve allotransplantation, serum samples were collected for miRNA expression analysis by Illumina small RNA deep sequencing.
  
  
  RESULTS
  Sequence analysis showed that the dominant size of circulating small RNAs after nerve allotransplantation was 22 nucleotides, followed by 23-nucleotide sequences. Nine upregulated circulating miRNAs (let-7e-5p, miR-101a-3p, miR-151-5p, miR-181a-5p, miR-204-5p, miR-340-5p, miR-381-3p, miR-411-5p, miR-9-5p, and miR-219-2-3p) were identified at 3 d, but none was identified at 7 or 14 d. Among them, miR-9-5p had the highest fold-change of >50-fold, followed by miR-340-5p with 38.8-fold. The presence of these nine miRNAs was not significant at 7 and 14 d after nerve allotransplantation with or without immunosuppression, showing that these miRNAs are not ideal biomarkers for monitoring rejection of deep-buried nerve allografts, a response usually observed later.
  
  
  CONCLUSIONS
  We identified nine upregulated circulating miRNAs, which may have a biological function, particularly during the early stages after nerve allotransplantation under FK506 immunosuppression.
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Cheng-Shyuan
authors.initials: CS
authors.lastname: Rau
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Johnson Chia-Shen
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Tsu-Hsiang
authors.initials: TH
authors.lastname: Lu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Yi-Chan
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Siou-Ling
authors.initials: SL
authors.lastname: Tzeng
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung 833, Taiwan.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Hsieh
mesh_terms: D064591:Allografts / Q000637:transplantation*; D000818:Animals; D059014:High-Throughput Nucleotide Sequencing; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D012584:Sciatic Nerve / Q000637:transplantation*; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D035683:MicroRNAs; D016559:Tacrolimus