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MicroRNAs are potential objective and early biomarkers for acute rejection of transplanted limbs in a rat model
Author(s) -
Oda Hiroki,
Ikeguchi Ryosuke,
Aoyama Tomoki,
Ohta Souichi,
Noguchi Takashi,
Kaizawa Yukitoshi,
Yurie Hirofumi,
Takeuchi Hisataka,
Yamamoto Koji,
Matsuda Shuichi
Publication year - 2017
Publication title -
microsurgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 63
eISSN - 1098-2752
pISSN - 0738-1085
DOI - 10.1002/micr.30236
Subject(s) - medicine , microrna , transplantation , downregulation and upregulation , biomarker , surgery , pathology , urology , biochemistry , chemistry , gene
Abstract Background Limb transplantation is considered to be a treatment option for amputees. Visual skin inspection and histological assessment are used to assess rejection, but these techniques are largely subjective. Using a rat model, we examined the potential of several microRNAs (miRNAs) to be used as objective and minimally invasive biomarkers of acute rejection of transplanted limbs. Methods Three Brown Norway rats and 15 Lewis rats were assigned to 2 groups. In the allograft group, 3 Brown Norway rats were used as the donors and 6 Lewis rats as the recipients. In the syngeneic (control) group, 9 Lewis rats were used as the donors and recipients. The hind limbs of the donors were orthotopically transplanted to the recipients. Plasma samples were obtained from all recipients before surgery and on posttransplantation days 3, 7, 10, and 14. All recipients were euthanized on day 14, and skin tissues were harvested for histological assessment. Results On posttransplantation days 10 and 14, the plasma expression of miRNA‐146a, miRNA‐155, and miRNA‐182 was significantly upregulated in the allograft group compared with the syngeneic control group. Of these 3 miRNAs, miRNA‐182 had the highest sensitivity and specificity; however the cutoff point for miRNA‐182 was close to the baseline and miRNA‐155 was considered to be most suitable for identifying rejection. Most skin samples in the allograft group were classified as exhibiting grade III rejection on day 14. Conclusions Some miRNAs are upregulated during acute rejection of transplanted limbs. These miRNAs are potential biomarkers for the objective, early, minimally invasive diagnosis of rejection.