miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages
IntroductionMacrophages play fundamental roles in immune regulation and tissue homeostasis, serving as one of the primary cell types that orchestrate tissue repair after injury. MiR-210 is a hypoxia-inducible, small non-coding RNA involved in regulating metabolic adaptation and inflammatory response...
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Frontiers Media S.A.
2025-08-01
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| author | Carmen Alexandra Neculachi Evelyn-Gabriela Nastase-Rusu Laudy Cherry Catalina Iolanda Marinescu-Colan Spyros Tastsoglou Bogdan Paul Cosman Alina Madalina Popa Cristina Panciuc Germana Zaccagnini Germana Zaccagnini Sergiu Bogdan Catrina Sergiu Bogdan Catrina Maya Simionescu Fabio Martelli Fabio Martelli Mihai Bogdan Preda Alexandrina Burlacu |
| author_facet | Carmen Alexandra Neculachi Evelyn-Gabriela Nastase-Rusu Laudy Cherry Catalina Iolanda Marinescu-Colan Spyros Tastsoglou Bogdan Paul Cosman Alina Madalina Popa Cristina Panciuc Germana Zaccagnini Germana Zaccagnini Sergiu Bogdan Catrina Sergiu Bogdan Catrina Maya Simionescu Fabio Martelli Fabio Martelli Mihai Bogdan Preda Alexandrina Burlacu |
| author_sort | Carmen Alexandra Neculachi |
| collection | DOAJ |
| description | IntroductionMacrophages play fundamental roles in immune regulation and tissue homeostasis, serving as one of the primary cell types that orchestrate tissue repair after injury. MiR-210 is a hypoxia-inducible, small non-coding RNA involved in regulating metabolic adaptation and inflammatory responses during normal repair processes. However, its role in macrophage polarization is not fully understood. Here, we report the impact of miR-210 deletion on macrophage polarization towards a pro-reparatory phenotype.MethodsBone marrow-derived macrophages were obtained from miR-210 knockout (KO) and wild-type (WT) mice and polarized toward the pro-reparative M2 phenotype. The transcriptomic profile of these cells, as well as their phagocytic capacity, cell energy phenotype, and cytokine production were assessed to determine the impact of miR-210 on the macrophage polarization process into a M2-like phenotype.ResultsCompared with their WT counterparts, miR-210 KO M0 macrophages presented a reduced glycolytic activity and a diminished metabolic flexibility. However, miR-210 KO cells exhibited increased phagocytosis in both M0 and M2 states, potentially as an adaptive response to their metabolic limitations. Transcriptomic analysis revealed distinct clustering between the M0 and M2 states, along with several notable differences in the transcriptional patterns between the two genotypes. Analysis of differentially expressed genes indicated an increased pro-inflammatory state in resting miR-210 KO macrophages compared to WT control cells. These data were further confirmed by the higher levels of IL-6, TNF-α, and IL-1b secreted by miR-210 KO M0 macrophages compared to WT cells. Analysis of the biological processes activated during the polarization process towards the M2 phenotype revealed an incomplete polarization of miR-210 KO cells, which may be attributed, at least in part, to reduced activation of mitotic regulators, leading to slower cell cycle progression and diminished proliferation.DiscussionOur data offers new insights into the role of miR-210 in promoting a macrophage shift toward the anti-inflammatory, pro-reparative M2 phenotype. The fine-tuned involvement of miR-210 in immune responses may have potential implications for chronic inflammation, immune dysfunction, and tissue repair. |
| format | Article |
| id | doaj-art-c57a11f82b1748b5aa01b1391e3c55eb |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-c57a11f82b1748b5aa01b1391e3c55eb2025-08-20T04:00:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16331631633163miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophagesCarmen Alexandra Neculachi0Evelyn-Gabriela Nastase-Rusu1Laudy Cherry2Catalina Iolanda Marinescu-Colan3Spyros Tastsoglou4Bogdan Paul Cosman5Alina Madalina Popa6Cristina Panciuc7Germana Zaccagnini8Germana Zaccagnini9Sergiu Bogdan Catrina10Sergiu Bogdan Catrina11Maya Simionescu12Fabio Martelli13Fabio Martelli14Mihai Bogdan Preda15Alexandrina Burlacu16Department of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaMolecular Cardiology Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, ItalyDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaMolecular Cardiology Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, ItalyDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, SwedenCenter for Diabetes, Academic Specialist Centrum, Stockholm, SwedenDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaMolecular Cardiology Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, ItalyDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaDepartment of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest, Bucharest, RomaniaIntroductionMacrophages play fundamental roles in immune regulation and tissue homeostasis, serving as one of the primary cell types that orchestrate tissue repair after injury. MiR-210 is a hypoxia-inducible, small non-coding RNA involved in regulating metabolic adaptation and inflammatory responses during normal repair processes. However, its role in macrophage polarization is not fully understood. Here, we report the impact of miR-210 deletion on macrophage polarization towards a pro-reparatory phenotype.MethodsBone marrow-derived macrophages were obtained from miR-210 knockout (KO) and wild-type (WT) mice and polarized toward the pro-reparative M2 phenotype. The transcriptomic profile of these cells, as well as their phagocytic capacity, cell energy phenotype, and cytokine production were assessed to determine the impact of miR-210 on the macrophage polarization process into a M2-like phenotype.ResultsCompared with their WT counterparts, miR-210 KO M0 macrophages presented a reduced glycolytic activity and a diminished metabolic flexibility. However, miR-210 KO cells exhibited increased phagocytosis in both M0 and M2 states, potentially as an adaptive response to their metabolic limitations. Transcriptomic analysis revealed distinct clustering between the M0 and M2 states, along with several notable differences in the transcriptional patterns between the two genotypes. Analysis of differentially expressed genes indicated an increased pro-inflammatory state in resting miR-210 KO macrophages compared to WT control cells. These data were further confirmed by the higher levels of IL-6, TNF-α, and IL-1b secreted by miR-210 KO M0 macrophages compared to WT cells. Analysis of the biological processes activated during the polarization process towards the M2 phenotype revealed an incomplete polarization of miR-210 KO cells, which may be attributed, at least in part, to reduced activation of mitotic regulators, leading to slower cell cycle progression and diminished proliferation.DiscussionOur data offers new insights into the role of miR-210 in promoting a macrophage shift toward the anti-inflammatory, pro-reparative M2 phenotype. The fine-tuned involvement of miR-210 in immune responses may have potential implications for chronic inflammation, immune dysfunction, and tissue repair.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1633163/fullmiR-210macrophagespolarizationinflammationmetabolismcell cycle |
| spellingShingle | Carmen Alexandra Neculachi Evelyn-Gabriela Nastase-Rusu Laudy Cherry Catalina Iolanda Marinescu-Colan Spyros Tastsoglou Bogdan Paul Cosman Alina Madalina Popa Cristina Panciuc Germana Zaccagnini Germana Zaccagnini Sergiu Bogdan Catrina Sergiu Bogdan Catrina Maya Simionescu Fabio Martelli Fabio Martelli Mihai Bogdan Preda Alexandrina Burlacu miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages Frontiers in Immunology miR-210 macrophages polarization inflammation metabolism cell cycle |
| title | miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages |
| title_full | miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages |
| title_fullStr | miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages |
| title_full_unstemmed | miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages |
| title_short | miR-210 promotes the anti-inflammatory phenotype and M2 polarization in murine macrophages |
| title_sort | mir 210 promotes the anti inflammatory phenotype and m2 polarization in murine macrophages |
| topic | miR-210 macrophages polarization inflammation metabolism cell cycle |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1633163/full |
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