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Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury

Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis‐induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influ...

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Autores principales: Juan, Chen‐Xia, Mao, Yan, Cao, Qian, Chen, Yan, Zhou, Lan‐Bo, Li, Sheng, Chen, Hao, Chen, Jia‐He, Zhou, Guo‐Ping, Jin, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107088/
https://www.ncbi.nlm.nih.gov/pubmed/33745232
http://dx.doi.org/10.1111/jcmm.16449
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author Juan, Chen‐Xia
Mao, Yan
Cao, Qian
Chen, Yan
Zhou, Lan‐Bo
Li, Sheng
Chen, Hao
Chen, Jia‐He
Zhou, Guo‐Ping
Jin, Rui
author_facet Juan, Chen‐Xia
Mao, Yan
Cao, Qian
Chen, Yan
Zhou, Lan‐Bo
Li, Sheng
Chen, Hao
Chen, Jia‐He
Zhou, Guo‐Ping
Jin, Rui
author_sort Juan, Chen‐Xia
collection PubMed
description Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis‐induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme‐linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR‐93‐5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin–interacting protein (TXNIP) was a direct target of miR‐93‐5p. Further in vitro and in vivo experiments indicated that exosomal miR‐93‐5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis‐induced AKI.
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spelling pubmed-81070882021-05-10 Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury Juan, Chen‐Xia Mao, Yan Cao, Qian Chen, Yan Zhou, Lan‐Bo Li, Sheng Chen, Hao Chen, Jia‐He Zhou, Guo‐Ping Jin, Rui J Cell Mol Med Original Articles Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis‐induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme‐linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR‐93‐5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin–interacting protein (TXNIP) was a direct target of miR‐93‐5p. Further in vitro and in vivo experiments indicated that exosomal miR‐93‐5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis‐induced AKI. John Wiley and Sons Inc. 2021-03-21 2021-05 /pmc/articles/PMC8107088/ /pubmed/33745232 http://dx.doi.org/10.1111/jcmm.16449 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Juan, Chen‐Xia
Mao, Yan
Cao, Qian
Chen, Yan
Zhou, Lan‐Bo
Li, Sheng
Chen, Hao
Chen, Jia‐He
Zhou, Guo‐Ping
Jin, Rui
Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury
title Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury
title_full Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury
title_fullStr Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury
title_full_unstemmed Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury
title_short Exosome‐mediated pyroptosis of miR‐93‐TXNIP‐NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis‐induced acute kidney injury
title_sort exosome‐mediated pyroptosis of mir‐93‐txnip‐nlrp3 leads to functional difference between m1 and m2 macrophages in sepsis‐induced acute kidney injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107088/
https://www.ncbi.nlm.nih.gov/pubmed/33745232
http://dx.doi.org/10.1111/jcmm.16449
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