Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Yiwen, Wu, Meifei, Xu, Lei, Cheng, Jieling, Shen, Jie, Yang, Tianyu, Zhang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783672281436782592
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
work_keys_str_mv AT zhouyiwen bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease
AT wumeifei bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease
AT xulei bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease
AT chengjieling bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease
AT shenjie bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease
AT yangtianyu bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease
AT zhanglei bmal1regulatesmacrophagepolarizethroughglycolyticpathwayinalcoholicliverdisease