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Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
Published on: January 7, 2019
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Macrophage transcriptome modification induced by hypoxia and lactate.
Yang Zhao1,2, Bin Zhao3, Xin Wang1
1Department of Transplantation, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Experimental and Therapeutic Medicine
|December 5, 2019
Summary
Lactate and hypoxia together strongly promote M2 macrophage polarization, impacting tumor microenvironments. This occurs via hypoxia-inducible factor 1 (HIF-1), Hedgehog, and mTOR pathways, influencing macrophage behavior.
Area of Science:
- Immunology
- Cancer Biology
- Bioinformatics
Background:
- Lactate production by cancer cells or under hypoxia is linked to M2 macrophage polarization.
- The precise role of lactate on macrophages, especially in hypoxia, requires further elucidation.
Purpose of the Study:
- To investigate the effects of lactate and hypoxia on macrophage gene expression and polarization using bioinformatics.
- To identify key signaling pathways involved in lactate- and hypoxia-induced macrophage responses.
Main Methods:
- Bioinformatics analysis of transcriptome data from macrophages under lactate, hypoxia, and combined conditions.
- Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-expression Network Analysis (WGCNA).
Main Results:
- Significant upregulation and downregulation of genes were observed in response to lactate and hypoxia.
- Differentially expressed genes were enriched in hypoxia-inducible factor 1 (HIF-1) and Hedgehog signaling pathways.
- Combined lactate and hypoxia markedly promoted M2 macrophage polarization via HIF-1, Hedgehog, and mTOR pathways, while lactate alone had minimal effect.
Conclusions:
- Lactate and hypoxia synergistically drive M2 macrophage polarization through specific signaling pathways.
- These combined factors may shape tumor microenvironments by modulating macrophage proliferation and recruitment.
