Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype
Abstract Macrophage plasticity is critical for maintaining immune function and developing solid tumors; however, the macrophage polarization mechanism remains incompletely understood. Our findings reveal that Mg2+ entry through distinct plasma membrane channels is critical to macrophage plasticity....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00815-x |
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| author | Viviane Nascimento Da Conceicao Yuyang Sun Manigandan Venkatesan Jorge De La Chapa Chapa Karthik Ramachandran Rahul S. Jasrotia Victor Drel Xiufang Chai Bibhuti B. Mishra Muniswamy Madesh Brij B. Singh |
| author_facet | Viviane Nascimento Da Conceicao Yuyang Sun Manigandan Venkatesan Jorge De La Chapa Chapa Karthik Ramachandran Rahul S. Jasrotia Victor Drel Xiufang Chai Bibhuti B. Mishra Muniswamy Madesh Brij B. Singh |
| author_sort | Viviane Nascimento Da Conceicao |
| collection | DOAJ |
| description | Abstract Macrophage plasticity is critical for maintaining immune function and developing solid tumors; however, the macrophage polarization mechanism remains incompletely understood. Our findings reveal that Mg2+ entry through distinct plasma membrane channels is critical to macrophage plasticity. Naïve macrophages displayed a previously unidentified Mg2+ dependent current, and TRPM7-like activity, which modulates its survival. Significantly, in M1 macrophages, Mg2+ entry is facilitated by a novel Mg²-dependent current that relies on extracellular Mg2+, which was crucial for activating iNOS/NFκB pathways and cellular bioenergetics, which drives pro-inflammatory cytokines. Conversely, in M2 macrophages, Mg2+ entry occurs primarily through TRPM7 channels, pivotal for IL-4 and IL-10-mediated anti-inflammatory cytokine secretion. Notably, the Mg2+ deficient diet or addition of TRPM7 agonist Naltriben suppresses the M1 phenotype while promoting angiogenic factors and fostering tumor growth. These findings suggest that Mg2+ flux via specific channels is indispensable for macrophage polarization, with its dysregulation playing a pivotal role in tumor progression. |
| format | Article |
| id | doaj-art-b03fb7a49bdb42b980c56d3c9f820921 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-b03fb7a49bdb42b980c56d3c9f8209212025-02-02T12:06:37ZengNature Portfolionpj Precision Oncology2397-768X2025-01-019111410.1038/s41698-025-00815-xNaltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotypeViviane Nascimento Da Conceicao0Yuyang Sun1Manigandan Venkatesan2Jorge De La Chapa Chapa3Karthik Ramachandran4Rahul S. Jasrotia5Victor Drel6Xiufang Chai7Bibhuti B. Mishra8Muniswamy Madesh9Brij B. Singh10Department of Periodontics, University of Texas Health San AntonioDepartment of Periodontics, University of Texas Health San AntonioCenter for Mitochondrial Medicine, Department of Medicine/Cardiology Division, University of Texas Health San AntonioDepartment of Periodontics, University of Texas Health San AntonioCenter for Mitochondrial Medicine, Department of Medicine/Cardiology Division, University of Texas Health San AntonioDepartment of Developmental Dentistry, University of Texas Health San AntonioDepartment of Periodontics, University of Texas Health San AntonioDepartment of Periodontics, University of Texas Health San AntonioDepartment of Developmental Dentistry, University of Texas Health San AntonioCenter for Mitochondrial Medicine, Department of Medicine/Cardiology Division, University of Texas Health San AntonioDepartment of Periodontics, University of Texas Health San AntonioAbstract Macrophage plasticity is critical for maintaining immune function and developing solid tumors; however, the macrophage polarization mechanism remains incompletely understood. Our findings reveal that Mg2+ entry through distinct plasma membrane channels is critical to macrophage plasticity. Naïve macrophages displayed a previously unidentified Mg2+ dependent current, and TRPM7-like activity, which modulates its survival. Significantly, in M1 macrophages, Mg2+ entry is facilitated by a novel Mg²-dependent current that relies on extracellular Mg2+, which was crucial for activating iNOS/NFκB pathways and cellular bioenergetics, which drives pro-inflammatory cytokines. Conversely, in M2 macrophages, Mg2+ entry occurs primarily through TRPM7 channels, pivotal for IL-4 and IL-10-mediated anti-inflammatory cytokine secretion. Notably, the Mg2+ deficient diet or addition of TRPM7 agonist Naltriben suppresses the M1 phenotype while promoting angiogenic factors and fostering tumor growth. These findings suggest that Mg2+ flux via specific channels is indispensable for macrophage polarization, with its dysregulation playing a pivotal role in tumor progression.https://doi.org/10.1038/s41698-025-00815-x |
| spellingShingle | Viviane Nascimento Da Conceicao Yuyang Sun Manigandan Venkatesan Jorge De La Chapa Chapa Karthik Ramachandran Rahul S. Jasrotia Victor Drel Xiufang Chai Bibhuti B. Mishra Muniswamy Madesh Brij B. Singh Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype npj Precision Oncology |
| title | Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype |
| title_full | Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype |
| title_fullStr | Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype |
| title_full_unstemmed | Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype |
| title_short | Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype |
| title_sort | naltriben promotes tumor growth by activating the trpm7 mediated development of the anti inflammatory m2 phenotype |
| url | https://doi.org/10.1038/s41698-025-00815-x |
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