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Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease
Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006279/ https://www.ncbi.nlm.nih.gov/pubmed/33790796 http://dx.doi.org/10.3389/fphar.2021.640521 |
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author | Zhou, Yiwen Wu, Meifei Xu, Lei Cheng, Jieling Shen, Jie Yang, Tianyu Zhang, Lei |
author_facet | Zhou, Yiwen Wu, Meifei Xu, Lei Cheng, Jieling Shen, Jie Yang, Tianyu Zhang, Lei |
author_sort | Zhou, Yiwen |
collection | PubMed |
description | Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. In vitro, blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What’s more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD. |
format | Online Article Text |
id | pubmed-8006279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80062792021-03-30 Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease Zhou, Yiwen Wu, Meifei Xu, Lei Cheng, Jieling Shen, Jie Yang, Tianyu Zhang, Lei Front Pharmacol Pharmacology Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. In vitro, blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What’s more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD. Frontiers Media S.A. 2021-03-10 /pmc/articles/PMC8006279/ /pubmed/33790796 http://dx.doi.org/10.3389/fphar.2021.640521 Text en Copyright © 2021 Zhou, Wu, Xu, Cheng, Shen, Yang and Zhang. http://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 | Pharmacology Zhou, Yiwen Wu, Meifei Xu, Lei Cheng, Jieling Shen, Jie Yang, Tianyu Zhang, Lei Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease |
title | Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease |
title_full | Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease |
title_fullStr | Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease |
title_full_unstemmed | Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease |
title_short | Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease |
title_sort | bmal1 regulates macrophage polarize through glycolytic pathway in alcoholic liver disease |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006279/ https://www.ncbi.nlm.nih.gov/pubmed/33790796 http://dx.doi.org/10.3389/fphar.2021.640521 |
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