- 作者: Cheng-Shyuan Rau, Johnson Chia-Shen Yang, Shao-Chun Wu, Yi-Chun Chen, Tsu-Hsiang Lu, Ming-Wei Lin, Yi-Chan Wu, Siou-Ling Tzeng, Chia-Jung Wu and Ching-Hua Hsieh
- 作者服務機構: Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123, Ta-Pei Road, Niao-Sung District, Kaohsiung City 833, Taiwan, R.O.C
- 中文摘要: --
- 英文摘要:
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 [rightwards arrow] Balb/c), (2) untreated allograft (C57BL/6 [rightwards arrow] Balb/c), and (3) allograft (C57BL/6 [rightwards arrow] 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. - 中文關鍵字: --
- 英文關鍵字: microRNAs (miRNAs), Circulating microRNAs, Nerve allotransplantation, FK506