title: Profiling circulating microRNA expression in a mouse model of nerve allotransplantation.
abstract: BACKGROUND
  The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression.
  
  
  RESULTS
  Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative real-time PCR (qRT-PCR). Three circulating miRNAs (miR-320, miR-762, and miR-423-5p) were identified in the whole blood and serum of the mice receiving an allograft with FK506 immunosuppression, within 2 weeks after nerve allotransplantation. However, these 3 circulating miRNAs were not expressed in the nerve grafts. The expression of all these 3 upregulated circulating miRNAs significantly decreased at 2, 4, and 6 d after discontinuation of FK506 immunosuppression. In the nerve graft, miR-125-3b and miR-672 were significantly upregulated in the mice that received an allograft with FK506 only at 7 d after nerve allotransplantation.
  
  
  CONCLUSIONS
  We identified the circulating miR-320, miR-762, and miR-423-5p as potential biomarkers for monitoring the immunosuppression status of the nerve allograft. However, further research is required to investigate the mechanism behind the dysregulation of these markers and to evaluate their prognostic value in nerve allotransplantation.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Center for Vascularized Composite Allotransplantation, No, 123, Ta-Pei Road, Kaohsiung City, Niao-Sung District, 833, Taiwan. m93chinghua@gmail.com.
authors.forename: Cheng-Shyuan
authors.initials: CS
authors.lastname: Rau
authors.forename: Johnson Chia-Shen
authors.initials: JC
authors.lastname: Yang
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Wu
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Tsu-Hsiang
authors.initials: TH
authors.lastname: Lu
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Yi-Chan
authors.initials: YC
authors.lastname: Wu
authors.forename: Siou-Ling
authors.initials: SL
authors.lastname: Tzeng
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Wu
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Hsieh
mesh_terms: D064591:Allografts / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000378:metabolism / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D035683:MicroRNAs