Figure - available from: BioMed Research International
This content is subject to copyright. Terms and conditions apply.
Source publication
We analyzed miRNA and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground-based rotating wall vessel (RWV) bioreactor. Our results show that 42 miRNAs were differentially expressed in MMG-incubated PBLs compared with 1 g incubated ones. Among these, miR-9-5p, miR-9-3p, miR...
Citations
... U937 myelomonocytic cells were also studied by Thiel .26030/sec3-y188) examined mRNA and miRNA expression profiles in peripheral blood lymphocytes (PBL) exposed to simulated microgravity through a miRNA-mRNA integration analysis, detecting effects on inflammatory response, apoptosis and cell proliferation decrease 59 . Let-7i, miR-7, miR-7-1, miR-27a, miR-144, miR-200a, miR-598, and miR-650 were found to be deregulated in human PBLs exposed to radiation and simulated microgravity (Rotating Wall Vessel) 60 . ...
One of the greatest challenges of humanity for deep space exploration is to fully understand how altered gravitational conditions affect human physiology. It is evident that the spaceflight environment causes multiple alterations to musculoskeletal, cardiovascular, immune and central nervous systems, to name a few known effects. To better characterize these biological effects, we compare gene expression datasets from microarray studies found in NASA GeneLab, part of the NASA Open Science Data Repository. In this review, we summarize these archived results for various tissues, emphasizing key genes which are highly reproducible in different mice or human experiments. Such exhaustive mining shows the potential of NASA Open Science data to identify and validate mechanisms taking place when mammalian organisms are exposed to microgravity or other spaceflight conditions. Our comparative meta-analysis findings highlight certain degrees of overlap and reproducibility in genes identified as differentially expressed within musculoskeletal tissues in each species across a variety of altered gravity conditions. However, the level of overlap between species was found to be significantly limited, partly attributed to the limited availability of human samples.
... Lastly, to assess the in uence of microgravity on the miRNA signature, we conducted miRNA expression analysis on OSD-55, an in vitro experiment performed on human peripheral blood lymphocytes (PBLs) under simulated microgravity conditions using a rotating wall vessel (RWV) bioreactor 32,33 . While these miRNAs are not derived from plasma like the SGA data and OSD-336, their inclusion is merited since they also circulate in the blood. ...
In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female health, potentially increasing risks for future pregnancies upon return to Earth, particularly related to small-for-gestational-age (SGA) fetuses. To address this, we identify a shared microRNA (miRNA) signature between SGA and the space environment, conserved across humans and mice. These miRNAs target genes and pathways relevant to diseases and development. Employing a machine learning approach, we identify potential FDA-approved drugs to mitigate these risks, including estrogen and progesterone receptor antagonists, vitamin D receptor antagonists, and DNA polymerase inhibitors. This study underscores potential pregnancy-related health risks for female astronauts and proposes pharmaceutical interventions to counteract the impact of space travel on female health.
... However, miRNAs have also been identi ed to play crucial roles in the regulation and prediction of various diseases, such as cancer 16 , neurodegenerative diseases 17,18 , autoimmune disorders 19 , and cardiovascular diseases 20,21 . In addition to that, previous studies have unveiled the in uence of microgravity 22,23 and ionizing radiation (IR) 23, 24 on miRNA expression. In modeled microgravity it has been shown that 42 miRNAs were dysregulated, most notably miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p that are also associated with genes involved in the in ammatory response, apoptosis and cell proliferation 22 . ...
... In addition to that, previous studies have unveiled the in uence of microgravity 22,23 and ionizing radiation (IR) 23, 24 on miRNA expression. In modeled microgravity it has been shown that 42 miRNAs were dysregulated, most notably miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p that are also associated with genes involved in the in ammatory response, apoptosis and cell proliferation 22 . Additionally, the combination of microgravity and IR was shown to alter let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 levels, suggesting a crucial role of miRNAs in cellular defense against oxidative and exogenous stress 23,24 . ...
... The limitations of our current study include the lack of observable histological brosis in mouse models and short exposure time under GCR or SPE radiation compared to longer space ight exposure time in other studies 22 . Our COL1 expression level analysis indicates the molecular change in brotic status in cardiac tissue after radiation, but no histological alteration was observed. ...
MicroRNAs (miRNAs) are small, non-coding RNA molecules that are post-transcriptional regulators of gene expression. miRNAs have been shown to be key regulators of complicated pathological processes and hence great biomarkers for the early prediction of diseases, such as cardiovascular diseases and radiation-associated alteration after spaceflight. In this study, we present possible antagomir treatments targeting three different miRNAs, miR-16-5p, miR-125b-5p, and let-7a-5p, to mitigate the activity of the spaceflight environment in cardiovascular diseases. We focus on three proteins of interest associated with fibrotic remodeling, TGF-β1, SMAD3, and COL1, analyzing the molecular outcomes of antagomir treatment when exposed to Galactic Cosmic Radiation (GCR), Solar Particle Events (SPE) radiation, and microgravity. These proteins have been shown to play different fibrotic and antifibrotic roles and show molecular changes associated with exposure to the space environment. Furthermore, our results demonstrate the therapeutic potential of antagomirs as a countermeasure for future spaceflight missions.
... MiRNAs targeting genes belonging to cell cycle and proliferation, DNA repair, apoptosis, and the Notch signaling pathway were found to be significantly altered in human colorectal cancer cells and lymphoblast leukemic cells incubated for 72 h in simulated microgravity with respect to the counterpart cultured cells in static 1 g [116]. A group of miRNA-mRNA pairs related to immunity, cell proliferation, and apoptosis were also identified in human PBLs incubated for 24 h in MMG [126]. Many of the genes and miRNAs found to be dysregulated are involved in biological processes of the immune/inflammatory response, signal transduction, regulation of response to stress, regulation of programmed cell death/proliferation, and the NF-kB pathway. ...
The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.
... There is evidence that exposure of lymphocytes to spaceflight as well as to simulated altered gravity conditions created by microgravity-simulating devices results in elevated apoptosis of immune cells (Prasad et al., 2020a). Lymphocytes cultured in simulated microgravity conditions exhibited elevated apoptosis and reduced cell proliferation (Girardi et al., 2014). Previous studies revealed that the rate of apoptosis in Jurkat T lymphocytes was increased in microgravity conditions (Lewis et al., 1998;Lewis, 2000, Battista et al., 2012), which was reflected in time-dependent release of apoptosis-related factors like Fas/APO1 in the culture medium during exposure of 2 d real microgravity aboard different space shuttle flights conditions (Lewis et al., 1998, Cubano andLewis, 2000). ...
Functioning as the outermost self-renewing protective layer of the human organism, skin protects against a multitude of harmful biological and physical stimuli. Consisting of ectodermal, mesenchymal, and neural crest-derived cell lineages, tissue homeostasis, and signal transduction are finely tuned through the interplay of various pathways. A health problem of astronauts in space is skin deterioration. Until today, wound healing has not been considered as a severe health concern for crew members. This can change with deep space exploration missions and commercial spaceflights together with space tourism. Albeit the molecular process of wound healing is not fully elucidated yet, there have been established significant conceptual gains and new scientific methods. Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. Experimental designs utilizing microgravity allow new insights into the role of apoptosis in wound healing. Furthermore, impaired wound healing in unloading conditions would depict a significant challenge in human-crewed exploration space missions. In this review, we provide an overview of alterations in the behavior of cutaneous cell lineages under microgravity in regard to the impact of apoptosis in wound healing. We discuss the current knowledge about wound healing in space and simulated microgravity with respect to apoptosis and available therapeutic strategies.
... A 2011 study examined the effects of simulated microgravity on the miRNA pro le of human lymphoblastic cells using a high aspect ratio vessel to model microgravity in space [39]. More recently, 42 miRNAs from cultured human blood lymphocytes from 12 healthy subjects were differentially expressed in microgravity stimulated cells compared to static cells, with resultant mRNA gene targets involved in in ammatory and apoptotic responses [40]. Malkani et al. elucidated the role of circulating microRNAs as both a potential biomarker for health risks associated with space ight and a countermeasure to mitigate the damage caused to the body by the space environment [41]. ...
Objective: Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and biomarker expression.
Approach and Results: The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers whose expression levels were altered after DI. 22 “DI/PI” related miRNA were identified, of which five have potential targets in the Wnt pathway associated with platelet biogenesis and function. These findings are supported by increased circulating Axin1 and DKK1.
Conclusions: Circulating biomarker and miRomic analysis implicates miRNA regulation of Wnt/Dkk1/AXIN1 axis in DI/PI induced primed platelet phenotype. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.
... The aforementioned results indicate that gravity is responsible for inhibiting the transactivation of key immediate early genes [31]. Girardi et al. (2014) used simulated microgravity via a ground-based rotating wall vessel bioreactor in order to analyze the expression profiles of miRNAs and mRNAs in human peripheral blood lymphocytes (PBL) [32]. Forty two miRNAs, among which miR-9-3p, miR-9-5p, miR-150-3p, miR-155-5p and miR-378-3p, were differentially expressed compared with 1 g of incubated PBLs. ...
... The aforementioned results indicate that gravity is responsible for inhibiting the transactivation of key immediate early genes [31]. Girardi et al. (2014) used simulated microgravity via a ground-based rotating wall vessel bioreactor in order to analyze the expression profiles of miRNAs and mRNAs in human peripheral blood lymphocytes (PBL) [32]. Forty two miRNAs, among which miR-9-3p, miR-9-5p, miR-150-3p, miR-155-5p and miR-378-3p, were differentially expressed compared with 1 g of incubated PBLs. ...
... These genes are involved in the immune response, apoptosis and cell proliferation. In particular, the classification of the correlated genes evidenced significant enrichment in the inflammatory response, signal transduction, regulation of programmed cell death, cell proliferation and response to stress [32]. In a recent report Chowdhury et al. also stated that microgravity induced differential expression in 370 transcripts related to the oxidative stress response, carbohydrate metabolism and regulation of transcription [33]. ...
Gravity constituted the only constant environmental parameter, during the evolutionary period of living matter on Earth. However, whether gravity has affected the evolution of species, and its impact is still ongoing. The topic has not been investigated in depth, as this would require frequent and long-term experimentations in space or an environment of altered gravity. In addition, each organism should be studied throughout numerous generations to determine the profound biological changes in evolution. Here, we review the significant abnormalities presented in the cardiovascular, immune, vestibular and musculoskeletal systems, due to altered gravity conditions. We also review the impact that gravity played in the anatomy of snakes and amphibians, during their evolution. Overall, it appears that gravity does not only curve the space–time continuum but the biological continuum, as well.
... The microRNA (miRNA) and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) exposed to the RVW revealed 42 differentially expressed miRNAs in simulated microgravity-incubated PBLs compared with 1 g controls [84]. Bioinformatic evaluations showed changes in biological processes, among others, in the stress response, apoptosis, and proliferation regulation. ...
... Bioinformatic evaluations showed changes in biological processes, among others, in the stress response, apoptosis, and proliferation regulation. Cell viability and apoptosis assays validated the data obtained by bioinformatic analyses: Lymphocytes cultured in simulated microgravity conditions exhibited elevated apoptosis and reduced cell proliferation [84]. ...
All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage. Space environmental conditions have been shown to influence apoptosis in various cell types. Apoptosis has important functions in morphogenesis, organ development, and wound healing. This review provides an overview of microgravity research platforms and apoptosis. The sections summarize the current knowledge of the impact of microgravity and cosmic radiation on cells with respect to apoptosis. Apoptosis-related microgravity experiments conducted with different mammalian model systems are presented. Recent findings in cells of the immune system, cardiovascular system, brain, eyes, cartilage, bone, gastrointestinal tract, liver, and pancreas, as well as cancer cells investigated under real and simulated microgravity conditions, are discussed. This comprehensive review indicates the potential of the space environment in biomedical research.
... Interestingly, the findings of our study are in part consistent with former findings of a reduction in cell proliferation and a higher rate of apoptosis of in vitro and in vivo studies on changes in miRNA expression following exposure to microgravity. In vitro an altered expression pattern of miRNAs in human peripheral blood lymphocytes was shown to increase apoptosis and decrease cell proliferation following exposure to microgravity 38 . A recent study reported a decrease in TGF-Beta response and a change in miRNA signature as potential regulators of weightlessness induced changes in rodents. ...
Understanding physiologic reactions to weightlessness is an indispensable requirement for safe human space missions. This study aims to analyse changes in the expression of circulating miRNAs following exposure to gravitational changes. Eight healthy volunteers (age: 24.5 years, male: 4, female: 4) were included. Each subject underwent 31 short-term phases of weightlessness and hypergravity induced by parabolic flight as a spaceflight analogue. At baseline, 1 and 24 h after parabolic flight, venous blood was withdrawn. Analysis of circulating miRNAs in serum was conducted by means of next generation sequencing. In total, 213 miRNAs were robustly detected (TPM > 5) by small RNA sequencing in all 24 samples. Four miRNAs evidenced a significant change in expression after adjusting for multiple testing. Only miR-223-3p showed a consistent significant decrease 24 h after parabolic flight compared to baseline values and values at 1 h after parabolic flight. miR-941 and miR-24-3p showed a significant decrease 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. miR-486-5p showed a significant increase 24 h after parabolic flight compared to 1 h after parabolic flight but not to baseline values. A target network analysis identified genes of the p53 signaling pathway and the cell cycle highly enriched among the targets of the four microRNAs. Our findings suggest cellular adaption to gravitational changes at the post-transcriptional level. Based on our results, we suggest a change in cell cycle regulation as potential explanation for adaptational changes observed in space missions.
... Caenorhabditis elegans is a powerful tool to determine expression and functions of miRNAs, and some works have implied involvement of miRNAs during regulating response to stresses or toxicants 7,36,37 . In this study, we identified 19 dysregulated miRNAs caused by simulated microgravity treatment in RCCS system at 30 rpm and for 24 h ( Fig. 1 and Table S1). ...
... Thus, the detected dysregulated miRNAs in nematodes raised useful clues to understand functions of some miRNAs in response to microgravity stress in humans. Previous study has indicated that the modeled microgravity could dysregulate the expressions of let-7i and let-7e in human peripheral blood hymphocytes 36 . Spaceflight could affect the expressions of let-7 family (let-7i, let-7f., let-7c, and let-7a) in human fibroblast cells 33 . ...
microRNAs (miRNAs) post-transcriptionally regulate the expression of targeted genes. We here systematically identify miRNAs in response to simulated microgravity based on both expressions and functional analysis in Caenorhabditis elegans. After simulated microgravity treatment, we observed that 19 miRNAs (16 down-regulated and 3 up-regulated) were dysregulated. Among these dysregulated miRNAs, let-7, mir-54, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 were required for the toxicity induction of simulated microgravity in suppressing locomotion behavior. In nematodes, alteration in expressions of let-7, mir-67, mir-85, mir-252, mir-354, mir-789, mir-2208, and mir-5592 mediated a protective response to simulated microgravity, whereas alteration in mir-54 expression mediated the toxicity induction of simulated microgravity. Moreover, among these candidate miRNAs, let-7 regulated the toxicity of simulated microgravity by targeting and suppressing SKN-1/Nrf protein. In the intestine, a signaling cascade of SKN-1/Nrf-GST-4/GST-5/GST-7 required for the control of oxidative stress was identified to act downstream of let-7 to regulate the toxicity of simulated microgravity. Our data demonstrated the crucial function of miRNAs in regulating the toxicity of simulated microgravity stress in organisms. Moreover, our results further provided an important molecular basis for epigenetic control of toxicity of simulated microgravity.
