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

BACKGROUND: T 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 co...

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Autores principales: Guo, Yiwen, Zhang, Yixi, Yu, Jia, Dong, Yuqi, Chen, Zhitao, Zhu, Chuchen, Hong, Xitao, Xie, Zhonghao, Zhang, Min, Wang, Shuai, Liang, Yichen, He, Xiaoshun, Ju, Weiqiang, Chen, Maogen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518384/
https://www.ncbi.nlm.nih.gov/pubmed/37753085
http://dx.doi.org/10.3389/fimmu.2023.1184409
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author Guo, Yiwen
Zhang, Yixi
Yu, Jia
Dong, Yuqi
Chen, Zhitao
Zhu, Chuchen
Hong, Xitao
Xie, Zhonghao
Zhang, Min
Wang, Shuai
Liang, Yichen
He, Xiaoshun
Ju, Weiqiang
Chen, Maogen
author_facet Guo, Yiwen
Zhang, Yixi
Yu, Jia
Dong, Yuqi
Chen, Zhitao
Zhu, Chuchen
Hong, Xitao
Xie, Zhonghao
Zhang, Min
Wang, Shuai
Liang, Yichen
He, Xiaoshun
Ju, Weiqiang
Chen, Maogen
author_sort Guo, Yiwen
collection PubMed
description BACKGROUND: T 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. METHODS: The 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. RESULTS: Lots 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. CONCLUSION: We 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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spelling pubmed-105183842023-09-26 Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice Guo, Yiwen Zhang, Yixi Yu, Jia Dong, Yuqi Chen, Zhitao Zhu, Chuchen Hong, Xitao Xie, Zhonghao Zhang, Min Wang, Shuai Liang, Yichen He, Xiaoshun Ju, Weiqiang Chen, Maogen Front Immunol Immunology BACKGROUND: T 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. METHODS: The 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. RESULTS: Lots 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. CONCLUSION: We 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. Frontiers Media S.A. 2023-09-11 /pmc/articles/PMC10518384/ /pubmed/37753085 http://dx.doi.org/10.3389/fimmu.2023.1184409 Text en Copyright © 2023 Guo, Zhang, Yu, Dong, Chen, Zhu, Hong, Xie, Zhang, Wang, Liang, He, Ju and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Guo, Yiwen
Zhang, Yixi
Yu, Jia
Dong, Yuqi
Chen, Zhitao
Zhu, Chuchen
Hong, Xitao
Xie, Zhonghao
Zhang, Min
Wang, Shuai
Liang, Yichen
He, Xiaoshun
Ju, Weiqiang
Chen, Maogen
Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice
title Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice
title_full Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice
title_fullStr Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice
title_full_unstemmed Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice
title_short Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice
title_sort novel cerna network construction associated with programmed cell death in acute rejection of heart allograft in mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518384/
https://www.ncbi.nlm.nih.gov/pubmed/37753085
http://dx.doi.org/10.3389/fimmu.2023.1184409
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