Cell polarization, migration and tissue repair: A promising field for future melatonin research
Polarization, migration and repair
Keywords:
Biobridge, cell migration, cell polarization, healing, infalammation, melatonin, sirtuins, stem cells, tissue repair
Abstract
Melatonin has been shown to support the repair of various tissue injuries. Wound healing is a complicated process that comprises several different cellular activities and regulation mechanisms, such as activation and programming of stem cells, interaction of different cell types, polarization of cells, especially concerning the alternative of pro- vs. anti-inflammatory behavior, migration of cells to the site of replacement, with guidance by other cells and modified extracellular matrix, as observed in the formation of biobridges. In most of these processes, melatonin acts as a decisive modulator, but details depend on tissue and cell types and have not been completely identified. Many aspects will require a considerable amount of work for understanding, in this context, the role of melatonin on a comprehensive basis. Moreover, the modulation of important cell properties has remained partially unknown or has only poorly considered in recent work. For instance, pro- or anti-inflammatory polarization of cells has been described in various cell types, not only in macrophages, in which melatonin is a major regulator, but also in microglia, in astrocytes and in neutrophils. Even in fibroblasts, polarization has been observed and concerns the alternative of inflammatory or fibrotic behavior. Notably, polarized cells that support healing in normal tissue seem to also protect tumors, whereas inflammatory phenotypes show antitumor activities. With regard to antitumor properties of melatonin, it seems necessary to clarify whether melatonin polarizes cells differently in the tumor microenvironment, compared to normal tissue, in which it promotes healing.
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14. Avila-Ponce de León U, Vázquez-Jiménez A, Matadamas-Guzman M, Pelayo R, Resendis-Antonio O (2021) Transcriptional and microenvironmental landscape of macrophage transition in cancer: A Boolean analysis. Front. Immunol. 12: 642842
15. Lanoix D, Lacasse AA, Reiter RJ, Vaillancourt C (2012) Melatonin: the smart killer: the human trophoblast as a model. Mol. Cell. Endocrinol. 348: 1-11.
16. Slominski A, Hardeland R, Zmijewski MA, Slominski SM, Reiter RJ, Paus R (2018) Melatonin: A cutaneous perspective on its production, metabolism, and functions. J. Invest. Dermatol. 138: 490-499.
17. Bjørklund G, Dadar M, Aaseth J, Chirumbolo S (2020) Thymosin β4: a multi-faceted tissue repair stimulating protein in heart injury. Curr. Med. Chem. 25: 6294-6305.
18. Liu W, Yu M, Xie D, Wang L, Ye C, Zhu Q, et al. (2020) Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res. Ther. 11: 259.
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20. Hardeland R (2021) Melatonin and microglia. Int. J. Mol. Sci. 22: 8296.
21. Reiter RJ, Sharma R, Tan D-X, Chuffa LGA, da Silva DGH, Slominski AT, et al. (2024) Dual sources of melatonin and evidence for different primary functions. Front. Endocrinol. (Lausanne) 15: 1414463.
22. Markus RP, Cecon E, Pires-Lapa MA (2013) Immune-pineal axis: nuclear factor kappaB (NF-kB) mediates the shift in the melatonin source from pinealocytes to immune competent cells. Int. J. Mol. Sci. 14: 10979-10997.
23. Markus RP, Fernandes PA, Kinker GS, da Silveira Cruz-Machado S, Marçola M (2018) Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes. Br. J. Pharmacol. 175: 3239-3250.
24. Markus RP, Sousa KS, da Silveira Cruz-Machado S, Fernandes PA, Ferreira ZS (2021) Possible role of pineal and extra-pineal melatonin in surveillance, immunity, and first-line defense. Int. J. Mol. Sci. 22: 12143.
25. Radio NM, Doctor JS, Witt-Enderby PA (2006) Melatonin enhances alkaline phosphatase activity in differentiating human adult mesenchymal stem cells grown in osteogenic medium via MT2 melatonin receptors and the MEK/ERK1/2 signaling cascade. J. Pineal Res. 40: 332-342.
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27. Lai M, Jin Z, Tang Q. Lu M (2017) Sustained release of melatonin from TiO2 nanotubes for modulating osteogenic differentiation of mesenchymal stem cells in vitro. J. Biomater. Sci. Polym. Ed. 28: 1651-1664.
28. Dong P, Gu X, Zhu G, Li M. Ma B, Zi Y (2018) Melatonin induces osteoblastic differentiation of mesenchymal stem cells and promotes fracture healing in a rat model of femoral fracture via neuropeptide Y/neuropeptide Y receptor Y1 signaling. Pharmacology 2018, 102: 272-280.
29. Maria S, Samsonraj RM, Munmun F, Glas J, Silvestros M, Kotlarczyk MP, et al. (2018) Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis. J. Pineal Res. 64: e12465.
30. Jiang T, Xia C, Chen X, Hu Y, Wang Y, Wu J, et al. (2019) Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the AMPK/beta-catenin signalling pathway. Stem Cell Res. Ther. 10: 408.
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Published
2024-07-18
How to Cite
[1]
Hardeland, R. 2024. Cell polarization, migration and tissue repair: A promising field for future melatonin research. Melatonin Research. 7, 2 (Jul. 2024), 120-133. DOI:https://doi.org/https://doi.org/10.32794/mr112500171.
Section
Reviews
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