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Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury

Background: Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biologi...

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Autores principales: Liu, Chao, Chi, Kun, Geng, Xiaodong, Hong, Quan, Mao, Zhi, Huang, Qi, Liu, Dong, Wang, Yiqin, Zhang, Ying, Zhou, Feihu, Cai, Guangyan, Chen, Xiangmei, Sun, Xuefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193099/
https://www.ncbi.nlm.nih.gov/pubmed/34124093
http://dx.doi.org/10.3389/fmed.2021.655787
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author Liu, Chao
Chi, Kun
Geng, Xiaodong
Hong, Quan
Mao, Zhi
Huang, Qi
Liu, Dong
Wang, Yiqin
Zhang, Ying
Zhou, Feihu
Cai, Guangyan
Chen, Xiangmei
Sun, Xuefeng
author_facet Liu, Chao
Chi, Kun
Geng, Xiaodong
Hong, Quan
Mao, Zhi
Huang, Qi
Liu, Dong
Wang, Yiqin
Zhang, Ying
Zhou, Feihu
Cai, Guangyan
Chen, Xiangmei
Sun, Xuefeng
author_sort Liu, Chao
collection PubMed
description Background: Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia–reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved. Methods: A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis. Results: No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation. Conclusions: Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.
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spelling pubmed-81930992021-06-12 Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury Liu, Chao Chi, Kun Geng, Xiaodong Hong, Quan Mao, Zhi Huang, Qi Liu, Dong Wang, Yiqin Zhang, Ying Zhou, Feihu Cai, Guangyan Chen, Xiangmei Sun, Xuefeng Front Med (Lausanne) Medicine Background: Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia–reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved. Methods: A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis. Results: No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation. Conclusions: Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI. Frontiers Media S.A. 2021-05-28 /pmc/articles/PMC8193099/ /pubmed/34124093 http://dx.doi.org/10.3389/fmed.2021.655787 Text en Copyright © 2021 Liu, Chi, Geng, Hong, Mao, Huang, Liu, Wang, Zhang, Zhou, Cai, Chen and Sun. 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 Medicine
Liu, Chao
Chi, Kun
Geng, Xiaodong
Hong, Quan
Mao, Zhi
Huang, Qi
Liu, Dong
Wang, Yiqin
Zhang, Ying
Zhou, Feihu
Cai, Guangyan
Chen, Xiangmei
Sun, Xuefeng
Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury
title Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury
title_full Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury
title_fullStr Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury
title_full_unstemmed Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury
title_short Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury
title_sort exogenous biological renal support improves kidney function in mice with rhabdomyolysis-induced acute kidney injury
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193099/
https://www.ncbi.nlm.nih.gov/pubmed/34124093
http://dx.doi.org/10.3389/fmed.2021.655787
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