Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, 410083 Changsha, Hunan, China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
Front Biosci (Landmark Ed). 2022 Sep 30;27(10):279. doi: 10.31083/j.fbl2710279.
This study aimed to investigate the mechanisms of acute rejection for vascularized composite allotransplantation (VCA) using microRNAs (miRNAs) differential expression in a VCA animal model.
Brown Norway rats were used as transplant donors and Lewis rats as VCA receptors. The changes were divided into different stages before and after transplantation in Lewis rats, and all appearance changes were recorded. Also, histological evaluations were performed on all recipients, and the expression of microRNAs was analyzed when acute immune rejection occurred. Then, we used GO and KEGG Pathway enrichment analyses to predict miRNA targets. Finally, differentially expressed miRNAs were detected by RT-qPCR.
Compared to pre-operation, 22 miRNAs were differentially expressed after operations. Among them, nine were upregulated, and 13 were downregulated in skin tissues. The RT-qPCR results revealed that rno-miR-340-5p and rno-miR-21-5p were significantly upregulated and enriched in the PI3K-Akt signaling pathway. Moreover, rno-miR-145-5p and rno-miR-195-5p were significantly downregulated, and most of their target genes were enriched in the Hippo signaling pathway. The histological evaluations showed that, after VCA, the skin tissue presented severe acute rejection.
The miRNAs rno-miR-340-5p, rno-miR-21-5p, rno-miR-145-5p, and rno-miR-195-5p were significantly regulated during VCA acute rejection, when the four miRNAs analyses were done on skin biopsies. These miRNAs might be potential biomarkers for objective, early, and minimally invasive rejection diagnosis.
本研究旨在通过血管化复合组织移植（VCA）动物模型中差异表达的 microRNAs（miRNAs）来探讨急性排斥反应的机制。
以棕褐裸鼠为移植供体，以 Lewis 大鼠为 VCA 受体。Lewis 大鼠在移植前后的变化分为不同阶段，记录所有外观变化。对所有受体进行组织学评估，并在发生急性免疫排斥时分析 microRNA 的表达。然后，我们使用 GO 和 KEGG 通路富集分析来预测 miRNA 靶标。最后，通过 RT-qPCR 检测差异表达的 miRNAs。
与术前相比，术后有 22 个 miRNAs 表达差异。其中，皮肤组织中有 9 个上调，13 个下调。RT-qPCR 结果显示 rno-miR-340-5p 和 rno-miR-21-5p 显著上调，并富集在 PI3K-Akt 信号通路中。此外，rno-miR-145-5p 和 rno-miR-195-5p 显著下调，其大多数靶基因富集在 Hippo 信号通路中。组织学评价显示，VCA 后皮肤组织出现严重急性排斥反应。
在 VCA 急性排斥反应过程中，rno-miR-340-5p、rno-miR-21-5p、rno-miR-145-5p 和 rno-miR-195-5p 这四个 miRNA 在皮肤活检中被显著调控，这些 miRNA 可能是客观、早期和微创排斥诊断的潜在生物标志物。
