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Macrophage transcriptome modification induced by hypoxia and lactate
The production of lactate under hypoxic conditions or by cancer cells was reported to promote the M2 polarization of tumor-associated macrophages. However, the exact effect of lactate on macrophages, particularly under hypoxic conditions, has remained largely elusive. In the present study, an in-dep...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878900/ https://www.ncbi.nlm.nih.gov/pubmed/31798707 http://dx.doi.org/10.3892/etm.2019.8164 |
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author | Zhao, Yang Zhao, Bin Wang, Xin Guan, Ge Xin, Yang Sun, Yan Dong Wang, Jian Hong Guo, Yuan Zang, Yun Jin |
author_facet | Zhao, Yang Zhao, Bin Wang, Xin Guan, Ge Xin, Yang Sun, Yan Dong Wang, Jian Hong Guo, Yuan Zang, Yun Jin |
author_sort | Zhao, Yang |
collection | PubMed |
description | The production of lactate under hypoxic conditions or by cancer cells was reported to promote the M2 polarization of tumor-associated macrophages. However, the exact effect of lactate on macrophages, particularly under hypoxic conditions, has remained largely elusive. In the present study, an in-depth bioinformatics analysis of previously published transcriptome data of macrophages was performed. A total of 6, 101 and 764 upregulated genes were identified in the lactate, hypoxia and hypoxia-lactate groups, respectively, whereas 4, 41 and 588 genes were downregulated in the same respective groups. Furthermore, differentially expressed genes (DEGs) of the hypoxia and hypoxia-lactate groups were significantly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway and the Hedgehog pathway. Upregulation of the mTOR and Hedgehog pathways in the hypoxia-lactate group was identified by gene set enrichment analysis. Furthermore, a set of HIF-1 pathway-associated genes was identified to be positively correlated with hypoxia using weighted gene co-expression network analysis. Lactate was indicated to inhibit the cell cycle in a hypoxia-independent manner. The DEGs of the hypoxia and hypoxia-lactate groups, including C-C motif chemokine receptor type 1 and 5, were enriched in the cytokine-cytokine receptor interaction pathway. In conclusion, under normoxic conditions, lactate exerted a weak effect on macrophages, while the combination of lactate and hypoxia markedly promoted the M2-polarization of macrophages via the HIF-1, Hedgehog and mTOR pathways. Lactate and hypoxia may also contribute to the formation of the spatial structure of tumor niches by inhibiting the proliferation of resident macrophages and by regulating the recruitment of peripheral macrophages. |
format | Online Article Text |
id | pubmed-6878900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-68789002019-12-03 Macrophage transcriptome modification induced by hypoxia and lactate Zhao, Yang Zhao, Bin Wang, Xin Guan, Ge Xin, Yang Sun, Yan Dong Wang, Jian Hong Guo, Yuan Zang, Yun Jin Exp Ther Med Articles The production of lactate under hypoxic conditions or by cancer cells was reported to promote the M2 polarization of tumor-associated macrophages. However, the exact effect of lactate on macrophages, particularly under hypoxic conditions, has remained largely elusive. In the present study, an in-depth bioinformatics analysis of previously published transcriptome data of macrophages was performed. A total of 6, 101 and 764 upregulated genes were identified in the lactate, hypoxia and hypoxia-lactate groups, respectively, whereas 4, 41 and 588 genes were downregulated in the same respective groups. Furthermore, differentially expressed genes (DEGs) of the hypoxia and hypoxia-lactate groups were significantly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway and the Hedgehog pathway. Upregulation of the mTOR and Hedgehog pathways in the hypoxia-lactate group was identified by gene set enrichment analysis. Furthermore, a set of HIF-1 pathway-associated genes was identified to be positively correlated with hypoxia using weighted gene co-expression network analysis. Lactate was indicated to inhibit the cell cycle in a hypoxia-independent manner. The DEGs of the hypoxia and hypoxia-lactate groups, including C-C motif chemokine receptor type 1 and 5, were enriched in the cytokine-cytokine receptor interaction pathway. In conclusion, under normoxic conditions, lactate exerted a weak effect on macrophages, while the combination of lactate and hypoxia markedly promoted the M2-polarization of macrophages via the HIF-1, Hedgehog and mTOR pathways. Lactate and hypoxia may also contribute to the formation of the spatial structure of tumor niches by inhibiting the proliferation of resident macrophages and by regulating the recruitment of peripheral macrophages. D.A. Spandidos 2019-12 2019-11-04 /pmc/articles/PMC6878900/ /pubmed/31798707 http://dx.doi.org/10.3892/etm.2019.8164 Text en Copyright: © Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhao, Yang Zhao, Bin Wang, Xin Guan, Ge Xin, Yang Sun, Yan Dong Wang, Jian Hong Guo, Yuan Zang, Yun Jin Macrophage transcriptome modification induced by hypoxia and lactate |
title | Macrophage transcriptome modification induced by hypoxia and lactate |
title_full | Macrophage transcriptome modification induced by hypoxia and lactate |
title_fullStr | Macrophage transcriptome modification induced by hypoxia and lactate |
title_full_unstemmed | Macrophage transcriptome modification induced by hypoxia and lactate |
title_short | Macrophage transcriptome modification induced by hypoxia and lactate |
title_sort | macrophage transcriptome modification induced by hypoxia and lactate |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878900/ https://www.ncbi.nlm.nih.gov/pubmed/31798707 http://dx.doi.org/10.3892/etm.2019.8164 |
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