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Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats
BACKGROUND: The development of effective immunosuppressive regimens has resulted in many cases of successful hand transplantation. Visual skin inspection and histological evaluation are used to assess the rejection of hand transplants, but these methods are largely subjective. In this study, we aime...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096435/ https://www.ncbi.nlm.nih.gov/pubmed/27826601 http://dx.doi.org/10.1097/TXD.0000000000000620 |
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author | Oda, Hiroki Ikeguchi, Ryosuke Yurie, Hirofumi Kaizawa, Yukitoshi Ohta, Souichi Yamamoto, Koji Aoyama, Tomoki Matsuda, Shuichi |
author_facet | Oda, Hiroki Ikeguchi, Ryosuke Yurie, Hirofumi Kaizawa, Yukitoshi Ohta, Souichi Yamamoto, Koji Aoyama, Tomoki Matsuda, Shuichi |
author_sort | Oda, Hiroki |
collection | PubMed |
description | BACKGROUND: The development of effective immunosuppressive regimens has resulted in many cases of successful hand transplantation. Visual skin inspection and histological evaluation are used to assess the rejection of hand transplants, but these methods are largely subjective. In this study, we aimed to determine the potential of microRNAs (miRNAs) as biomarkers for acute rejection in vascularized composite allotransplants. METHODS: In allograft group, 7 male Brown-Norway rats (RT1(n)) were used as donors and 13 male Lewis rats (RT1(l)) were used as recipients. In control group, 8 Lewis rats were used as donors and recipients. The hindlimbs of donor rats were transplanted orthotopically to recipient rats. Skin changes were noted daily. Skin biopsies were obtained from 5 recipients and evaluated histologically. Plasma samples were obtained from the other 8 recipients before transplant and 7, 10, and 14 days posttransplant and used to measure miRNA expression. RESULTS: Skin changes occurred at a mean of 11.0 days posttransplant. Rejection in most skin biopsies taken 7 and 10 days posttransplant was histologically classified as grade 0, whereas that in most biopsies taken 14 days posttransplant was classified as grade 3. We found that expression of miRNA-146a and miRNA-155 was significantly upregulated at 10 and 14 days posttransplant compared with that at 7 days posttransplant. In control group, there were no significant changes in plasma miRNAs expressions. CONCLUSIONS: The upregulation of plasma miRNA-146a and miRNA-155 was detected before the histological evaluation methods could diagnose complete rejection in the rat hindlimb transplantation model. Plasma miRNA-146a and miRNA-155 may be potential biomarkers of acute rejection after vascularized composite allotransplantation. |
format | Online Article Text |
id | pubmed-5096435 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-50964352016-11-08 Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats Oda, Hiroki Ikeguchi, Ryosuke Yurie, Hirofumi Kaizawa, Yukitoshi Ohta, Souichi Yamamoto, Koji Aoyama, Tomoki Matsuda, Shuichi Transplant Direct Hand and Composite Tissue Allotransplantation BACKGROUND: The development of effective immunosuppressive regimens has resulted in many cases of successful hand transplantation. Visual skin inspection and histological evaluation are used to assess the rejection of hand transplants, but these methods are largely subjective. In this study, we aimed to determine the potential of microRNAs (miRNAs) as biomarkers for acute rejection in vascularized composite allotransplants. METHODS: In allograft group, 7 male Brown-Norway rats (RT1(n)) were used as donors and 13 male Lewis rats (RT1(l)) were used as recipients. In control group, 8 Lewis rats were used as donors and recipients. The hindlimbs of donor rats were transplanted orthotopically to recipient rats. Skin changes were noted daily. Skin biopsies were obtained from 5 recipients and evaluated histologically. Plasma samples were obtained from the other 8 recipients before transplant and 7, 10, and 14 days posttransplant and used to measure miRNA expression. RESULTS: Skin changes occurred at a mean of 11.0 days posttransplant. Rejection in most skin biopsies taken 7 and 10 days posttransplant was histologically classified as grade 0, whereas that in most biopsies taken 14 days posttransplant was classified as grade 3. We found that expression of miRNA-146a and miRNA-155 was significantly upregulated at 10 and 14 days posttransplant compared with that at 7 days posttransplant. In control group, there were no significant changes in plasma miRNAs expressions. CONCLUSIONS: The upregulation of plasma miRNA-146a and miRNA-155 was detected before the histological evaluation methods could diagnose complete rejection in the rat hindlimb transplantation model. Plasma miRNA-146a and miRNA-155 may be potential biomarkers of acute rejection after vascularized composite allotransplantation. Lippincott Williams & Wilkins 2016-10-07 /pmc/articles/PMC5096435/ /pubmed/27826601 http://dx.doi.org/10.1097/TXD.0000000000000620 Text en Copyright © 2016 The Authors. Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Hand and Composite Tissue Allotransplantation Oda, Hiroki Ikeguchi, Ryosuke Yurie, Hirofumi Kaizawa, Yukitoshi Ohta, Souichi Yamamoto, Koji Aoyama, Tomoki Matsuda, Shuichi Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats |
title | Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats |
title_full | Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats |
title_fullStr | Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats |
title_full_unstemmed | Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats |
title_short | Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats |
title_sort | plasma micrornas are potential biomarkers of acute rejection after hindlimb transplantation in rats |
topic | Hand and Composite Tissue Allotransplantation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096435/ https://www.ncbi.nlm.nih.gov/pubmed/27826601 http://dx.doi.org/10.1097/TXD.0000000000000620 |
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