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Fujino, Masayuki; Zhu, Ping; Cai, Shanshan; Nishio, Yoshiaki; Zhuang, Jian; Li, Xiaokang

doi:10.6002/ect.2015.0251

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…MiRNAs are also closely related to transplantation immune rejection. miRNAs regulate the immune and inflammatory microenvironment in the recipient, and induce immune tolerance or rejection in the graft (9)(10)(11)(12)(13). Therefore, differential expression of miRNAs can be used to predict rejection after heart transplantation (14-19).…”

Section: Introductionmentioning

confidence: 99%

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice

Guo,

Zhang,

et al. 2023

Front. Immunol.

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BackgroundT cell-mediated acute rejection(AR) after heart transplantation(HT) ultimately results in graft failure and is a common indication for secondary transplantation. It’s a serious threat to heart transplant recipients. This study aimed to explore the novel lncRNA-miRNA-mRNA networks that contributed to AR in a mouse heart transplantation model.MethodsThe donor heart from Babl/C mice was transplanted to C57BL/6 mice with heterotopic implantation to the abdominal cavity. The control group was syngeneic heart transplantation with the same kind of mice donor. The whole-transcriptome sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in mouse heart allograft. The biological functions of ceRNA networks was analyzed by GO and KEGG enrichment. Differentially expressed ceRNA involved in programmed cell death were further verified with qRT-PCR testing.ResultsLots of DEmRNAs, DEmiRNAs and DElncRNAs were identified in acute rejection and control after heart transplantation, including up-regulated 4754 DEmRNAs, 1634 DElncRNAs, 182 DEmiRNAs, and down-regulated 4365 DEmRNAs, 1761 DElncRNAs, 132 DEmiRNAs. Based on the ceRNA theory, lncRNA-miRNA-mRNA regulatory networks were constructed in allograft acute rejection response. The functional enrichment analysis indicate that the down-regulated mRNAs are mainly involved in cardiac muscle cell contraction, potassium channel activity, etc. and the up-regulated mRNAs are mainly involved in T cell differentiation and mononuclear cell migration, etc. The KEGG pathway enrichment analysis showed that the down-regulated DEmRNAs were mainly enriched in adrenergic signaling, axon guidance, calcium signaling pathway, etc. The up-regulated DEmRNAs were enriched in the adhesion function, chemokine signaling pathway, apoptosis, etc. Four lncRNA-mediated ceRNA regulatory pathways, Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox, 1700071M16Rik/miR-145a-3p/Themis2, were finally validated. In addition, increased expression of PVT1, 1700071M16Rik, Tox and Themis2 may be considered as potential diagnostic gene biomarkers in AR.ConclusionWe speculated that Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox and 1700071M16Rik/miR-145a-3p/Themis2 interaction pairs may serve as potential biomarkers in AR after HT.

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Section: Introductionmentioning

confidence: 99%

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice

Guo,

Zhang,

et al. 2023

Front. Immunol.

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Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

et al. 2017

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Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection. Furthermore, in vitro study using human renal glomerular endothelial cells (HRGECs) transfected with a miR-650 mimic revealed that key characteristics of acute renal allograft rejection were observed, including apoptosis, the release of cytokines and the chemotaxis of macrophages, while the effects were reduced in HRGECs transfected with a miR-650 inhibitor. The existence of a conserved miR-650 binding site on the 3′-untranslated region of BCL11B mRNA was predicted by computational algorithms and confirmed by a luciferase reporter assay. Knockdown of BCL11B with small interfering RNA (siRNA) significantly increased the apoptotic rate and significantly decreased the proliferation ability of HRGECs compared with the negative control group. HRGECs transfected with a combination of BCL11B siRNA and the miR-650 mimic demonstrated a significant increase in the rate of apoptosis compared with the control. These results suggest that the upregulation of miR-650 contributes to the development of acute renal allograft rejection by suppression of BCL11B, which leads to apoptosis and inflammatory responses. Thus, miR-650 and BCL11B may represent potential therapeutic targets for the prevention of acute renal allograft rejection.

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MicroRNAs as theranostic markers in cardiac allograft transplantation: from murine models to clinical practice

et al. 2021

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Congestive heart failure affects about 23 million people worldwide, and cardiac allograft transplantation remains one of the last options for patients with terminal refractory heart failure. Besides the infectious or oncological complications, the prognosis of patients after heart transplantation is affected by acute cellular or antibody-mediated rejection and allograft vasculopathy development. Current monitoring of both conditions requires the performance of invasive procedures (endomyocardial biopsy sampling and coronary angiography or optical coherence tomography, respectively) that are costly, time-demanding, and non-comfortable for the patient. Within this narrative review, we focus on the potential pathophysiological and clinical roles of microRNAs (miRNAs, miRs) in the field of cardiac allograft transplantation. Firstly, we provide a general introduction about the status of cardiac allograft function monitoring and the discovery of miRNAs as post-transcriptional regulators of gene expression and clinically relevant biomarkers found in the extracellular fluid. After this general introduction, information from animal and human studies are summarized to underline the importance of miRNAs both in the pathophysiology of the rejection process, the possibility of its modulation by altering miRNAs levels, and last but not least, about the use of miRNAs in the clinical practice to diagnose or predict the rejection occurrence.

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Untitled

Cited by 3 publications

References 27 publications

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice

Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene expression following transplantation: A novel mechanism behind the acute rejection of renal allografts

MicroRNAs as theranostic markers in cardiac allograft transplantation: from murine models to clinical practice

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