Integration Analysis of MicroRNA and mRNA Expression Profiles in Human Peripheral Blood Lymphocytes Cultured in Modeled Microgravity

Girardi, Cristina; Pittà, Cristiano De; Casara, Silvia; Calura, Enrica; Romualdi, Chiara; Celotti, Lucia; Mognato, Maddalena

doi:10.1155/2014/296747

Cited by 39 publications

(45 citation statements)

References 97 publications

(108 reference statements)

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“…8 Together, data from the International Space Station, Skylab, and space shuttle suggest that dysregulated immune cell-mediated cytokine secretion is a major mechanism leading to spaceflightassociated immune dysfunction. 5,[9][10][11][12] For example, after space travel, shifts occur in circulating cytokines, including increased levels of T lymphocytes producing IL-4, IL-8, IL-17, and IFN-γ 8,13,14 and decreased production of IL-1, IL-6, IL-12, and TNF-α in monocytes/ macrophages. [15][16][17][18] However, the causes of these immune cell dysfunctions and the associated changes in innate (macrophages and NK cells) and adaptive (T-cell) functions have not been extensively and systematically examined.…”

Section: Introductionmentioning

confidence: 99%

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

et al. 2020

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Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

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Section: Introductionmentioning

confidence: 99%

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

et al. 2020

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“…S paceflight , in particular microgravity , changes the innate and adpative immune system in many aspects (1–3). For example, astronauts returning from spaceflights have neutrophilia and eosinopenia (4–6).…”

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confidence: 99%

“…SPACEFLIGHT, IN PARTICULAR MICROGRAVITY, CHANGES the innate and adpative immune system in many aspects (1)(2)(3). For example, astronauts returning from spaceflights have neutrophilia and eosinopenia (4)(5)(6).…”

mentioning

confidence: 99%

Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility

Li¹,

Shi²,

Zhang³

et al. 2015

The FASEB Journal

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The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.

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“…The gene and miRNA expression of HPBLs in microgravity and normal gravity were measured by microarray, which were performed by Girardi et al [ 63 ]. They obtained the HPBLs from five healthy donors, which were incubated in normal gravity and modeled microgravity for 24 h, respectively.…”

Section: Methodsmentioning

confidence: 99%

Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis

Yuan

Liu

Zhou

et al. 2020

IJMS

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Previous studies have demonstrated that microgravity could lead to health risks. The investigation of the molecular mechanisms from the aspect of systems biology has not been performed yet. Here, we integratively analyzed transcriptional and post-transcriptional regulations based on gene and miRNA expression profiles in human peripheral blood lymphocytes cultured in modeled microgravity. Two hundred and thirty dysregulated TF-miRNA (transcription factor and microRNA) feed-forward loops (FFLs) were identified in microgravity. The immune, cardiovascular, endocrine, nervous and skeletal system subnetworks were constructed according to the functions of dysregulated FFLs. Taking the skeletal system as an example, most of genes and miRNAs in the subnetwork were involved in bone loss. In addition, several drugs have been predicted to have potential to reduce bone loss, such as traditional Chinese medicines Emodin and Ginsenoside Rh2. Furthermore, we investigated the relationships between microgravity and 20 cancer types, and found that most of cancers might be promoted by microgravity. For example, rectum adenocarcinoma (READ) might be induced by microgravity through reducing antigen presentation and suppressing IgA-antibody-secreting cells’ migration. Collectively, TF-miRNA FFL might provide a novel mechanism to elucidate the changes induced by microgravity, serve as drug targets to relieve microgravity effects, and give new insights to explore the relationships between microgravity and cancers.

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Integration Analysis of MicroRNA and mRNA Expression Profiles in Human Peripheral Blood Lymphocytes Cultured in Modeled Microgravity

Cited by 39 publications

References 97 publications

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility

Integrative Analysis of Regulatory Module Reveals Associations of Microgravity with Dysfunctions of Multi-body Systems and Tumorigenesis

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