Version 1
: Received: 28 June 2022 / Approved: 7 July 2022 / Online: 7 July 2022 (04:08:39 CEST)
Version 2
: Received: 18 July 2022 / Approved: 18 July 2022 / Online: 18 July 2022 (10:59:36 CEST)
How to cite:
An, R. MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space . Preprints2022, 2022070106. https://doi.org/10.20944/preprints202207.0106.v1.
An, R. MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space . Preprints 2022, 2022070106. https://doi.org/10.20944/preprints202207.0106.v1.
Cite as:
An, R. MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space . Preprints2022, 2022070106. https://doi.org/10.20944/preprints202207.0106.v1.
An, R. MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space . Preprints 2022, 2022070106. https://doi.org/10.20944/preprints202207.0106.v1.
Abstract
Macrophages exhibit impaired phagocytosis, adhesion, migration, and cytokine production in space, hindering their ability to elicit immune responses. The combined effect of spaceflight microgravity and radiation on macrophage dysfunction is multiscale and multifactorial in nature. However, spaceflight and simulated microgravity experiments often take single-scale approaches. This hypothesis and theory paper reanalyzes research in the macrophage spaceflight response across multiple scales, from the molecular, intracellular, extracellular, to the physiological. Here, we introduce the time-dependent, mechanotransducive MRTF-A/SRF pathway, which depends on intracellular localization, to elucidate seemingly contradictory macrophage responses across time scales. We discuss the MRTF-A/SRF pathway dependence on the actin cytoskeleton/nucleoskeleton, microtubules, mechanosensitive membrane proteins, hypoxia, oxidative stress, and crosstalk with other pathways and cells. By adopting a multiscale perspective, this paper identifies potential mechanisms for adverse macrophage responses and strengthens the connection between microgravity, mechanobiology, and the spaceflight immune response. Finally, we hypothesize MRTF involvement and complications in treating spaceflight-induced cardiovascular, skeletal, and immune disease.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
