Potential Roles of miRNAs in Acute Rejection for Vascularized Composite Allotransplantation

Haibo Li; Yuan Fang; Xu Li; Jingting Chen; Yao Xiong; Yongzhou Shi; Shengli Li; Lincai Ye; Shoubao Wang; Jianda Zhou

doi:10.2147/JIR.S383628

Potential Roles of miRNAs in Acute Rejection for Vascularized Composite Allotransplantation

J Inflamm Res. 2022 Oct 28:15:6021-6030. doi: 10.2147/JIR.S383628. eCollection 2022.

Authors

Haibo Li^#^{1

2}, Yuan Fang^#^{1

2}, Xu Li^#², Jingting Chen¹, Yao Xiong¹, Yongzhou Shi³, Shengli Li¹, Lincai Ye⁴, Shoubao Wang^#¹, Jianda Zhou^#²

Affiliations

¹ Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
² Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
³ Department of Neurosurgery, Neihuang Chinese Medicine Hospital, Anyang, People's Republic of China.
⁴ Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

^# Contributed equally.

Abstract

Aim: The development of microsurgery has greatly advanced vascularized composite allotransplantation (VCA). However, like organ transplantation, VCA is also limited by acute rejection, and concerns regarding long-term survival and function of the transplanted graft. Therefore, it is necessary to elucidate the molecular mechanisms underlying acute rejection caused by VCA, in order to improve patient survival.

Methods: Firstly, we used Brown Norway rats and Lewis rats to construct animal model of VCA. Regularly record the appearance changes of all subjects. Specimens were collected for histological examination, microRNAs (miRNAs) sequencing and RT-qPCR verification when acute immune rejection occurred. Then, bioinformatics analysis was employed to predict miRNA related molecules and pathway information. Finally, differentially expressed miRNAs were tested and verified.

Results: MiRNAs are small non coding RNA transcripts that regulate gene expression at the post-transcriptional level. Studies have shown that miRNAs are involved in immune regulation and several miRNAs have been identified that are potential diagnostic and prognostic biomarkers of acute rejection. In this study, we found that the expression levels of rno-miR-21-5p, rno-miR-340-5p, rno-miR-1-3p and rno-miR-195-5p are significantly associated with acute rejection following VCA.

Conclusion: This miRNA signature can potentially an auxiliary diagnostic indicator of rejection, which can help clinicians adjust the immunosuppressive program in time during acute rejection.

Keywords: VCA2; acute rejection5; miRNAs4; vascularized composite tissue allograft1.

Grants and funding

This work was supported by a grant from National Major Science and Technology Projects of China (2018ZX10303502), Postdoctoral Science Foundation (2019T120347) and National Natural Science Foundation of China (82002065).