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Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury

BACKGROUND: Acute liver injury can occur at any stage of sepsis and is an important sign of multiple organ dysfunction syndrome (MODS). Studies have shown that agmatine (AGM) can effectively improve liver injury caused by sepsis. However, due to the numerous metabolites and metabolic pathways of AGM...

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Autores principales: Huang, Ling, Gan, Lianfang, Pan, Junhua, Zhong, Lifan, Wang, Qianru, Luo, Shanjun, Tian, Jia, Liang, Huaping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201151/
https://www.ncbi.nlm.nih.gov/pubmed/35722424
http://dx.doi.org/10.21037/atm-22-2103
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author Huang, Ling
Gan, Lianfang
Pan, Junhua
Zhong, Lifan
Wang, Qianru
Luo, Shanjun
Tian, Jia
Liang, Huaping
author_facet Huang, Ling
Gan, Lianfang
Pan, Junhua
Zhong, Lifan
Wang, Qianru
Luo, Shanjun
Tian, Jia
Liang, Huaping
author_sort Huang, Ling
collection PubMed
description BACKGROUND: Acute liver injury can occur at any stage of sepsis and is an important sign of multiple organ dysfunction syndrome (MODS). Studies have shown that agmatine (AGM) can effectively improve liver injury caused by sepsis. However, due to the numerous metabolites and metabolic pathways of AGM in the human body, its mechanism in treating septic liver injury is unclear. METHODS: In this study, a liver injury model of septic Sprague-Dawley rats was established by cecal ligation and perforation (CLP). After AGM treatment, transcriptomics combined with metabolomics was employed to analyze the gene expression levels and metabolite changes. RESULTS: The results showed that AGM decreased the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), procalcitonin (PCT), and inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] in the serum of septic rats. It also reduced liver inflammatory cell infiltration and abnormal lipid metabolism, and promoted the survival rate of septic rats. In addition, 17 differentially-expressed genes were identified by transcriptomics, mainly in arginine and proline metabolism, the arachidonic acid metabolism pathway, as well as the nuclear factor kappa B (NF-κB) and AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor α (PPARα) signal transduction pathways. Metabolomics analysis was carried out to study the potential liver metabolism spectrum changes induced by AGM treatment. The results showed significant changes in 26 metabolites in the rat liver samples, mainly involved in arginine and proline metabolism, arachidonic acid metabolism, linoleic acid metabolism, and fatty acid metabolism. CONCLUSIONS: The integrated transcriptomics and metabolomics analysis demonstrated that AGM improved septic liver injury by regulating lipid metabolism, and reduced the inflammatory reaction by affecting fatty acid metabolism, amino acid metabolism, and the arachidonic acid metabolism pathway. The integration of transcriptomics and metabolomics provides an effective means to elucidate AGM’s therapeutic pathways and biomarkers.
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spelling pubmed-92011512022-06-17 Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury Huang, Ling Gan, Lianfang Pan, Junhua Zhong, Lifan Wang, Qianru Luo, Shanjun Tian, Jia Liang, Huaping Ann Transl Med Original Article BACKGROUND: Acute liver injury can occur at any stage of sepsis and is an important sign of multiple organ dysfunction syndrome (MODS). Studies have shown that agmatine (AGM) can effectively improve liver injury caused by sepsis. However, due to the numerous metabolites and metabolic pathways of AGM in the human body, its mechanism in treating septic liver injury is unclear. METHODS: In this study, a liver injury model of septic Sprague-Dawley rats was established by cecal ligation and perforation (CLP). After AGM treatment, transcriptomics combined with metabolomics was employed to analyze the gene expression levels and metabolite changes. RESULTS: The results showed that AGM decreased the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), procalcitonin (PCT), and inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] in the serum of septic rats. It also reduced liver inflammatory cell infiltration and abnormal lipid metabolism, and promoted the survival rate of septic rats. In addition, 17 differentially-expressed genes were identified by transcriptomics, mainly in arginine and proline metabolism, the arachidonic acid metabolism pathway, as well as the nuclear factor kappa B (NF-κB) and AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor α (PPARα) signal transduction pathways. Metabolomics analysis was carried out to study the potential liver metabolism spectrum changes induced by AGM treatment. The results showed significant changes in 26 metabolites in the rat liver samples, mainly involved in arginine and proline metabolism, arachidonic acid metabolism, linoleic acid metabolism, and fatty acid metabolism. CONCLUSIONS: The integrated transcriptomics and metabolomics analysis demonstrated that AGM improved septic liver injury by regulating lipid metabolism, and reduced the inflammatory reaction by affecting fatty acid metabolism, amino acid metabolism, and the arachidonic acid metabolism pathway. The integration of transcriptomics and metabolomics provides an effective means to elucidate AGM’s therapeutic pathways and biomarkers. AME Publishing Company 2022-05 /pmc/articles/PMC9201151/ /pubmed/35722424 http://dx.doi.org/10.21037/atm-22-2103 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Huang, Ling
Gan, Lianfang
Pan, Junhua
Zhong, Lifan
Wang, Qianru
Luo, Shanjun
Tian, Jia
Liang, Huaping
Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
title Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
title_full Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
title_fullStr Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
title_full_unstemmed Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
title_short Transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
title_sort transcriptomics combined with metabolomics analysis of the mechanism of agmatine in the treatment of septic liver injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201151/
https://www.ncbi.nlm.nih.gov/pubmed/35722424
http://dx.doi.org/10.21037/atm-22-2103
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