Macrophage transcriptome modification induced by hypoxia and lactate
| Autor: | Yuan Guo, Yun Jin Zang, Ge Guan, Xin Wang, Yan Dong Sun, Yang Xin, Jianhong Wang, Bin Zhao, Yang Zhao |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research lactate Chemistry hypoxia General Medicine Articles macrophage Hypoxia (medical) Hedgehog signaling pathway Cell biology Transcriptome 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immunology and Microbiology (miscellaneous) Downregulation and upregulation Apoptosis 030220 oncology & carcinogenesis medicine cancer medicine.symptom Signal transduction Hedgehog PI3K/AKT/mTOR pathway |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-0981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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