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Recent Advances in Microgravity and Cell Adherence

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 13276

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Guest Editor
SiHaTho GmbH, Biedenkopf, Germany
Interests: cell adhesion; organoid formation; data evaluation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The adhesion behavior of many types of cells changes when gravity forces affecting these cells are modified during their growth in space or on special devices which change the gravity vector continuously. According to current knowledge, these changes are accompanied by alterations in quantities, localization, and/or posttranslational modification of a considerable number of proteins. In recent years, many attempts have been made to determine how the lack of the rather small force of 1g that pulls cells constantly to the center of the earth is transformed into physiological reactions which, together, induce an alteration in the behavior of whole cells. These efforts suggested a complicated interplay of changes in protein conformation, complex formation and enzymatic activities. However, this suggestion requires substantiation. It is of special interest to identify the various changes and observe how they are linked together. This will help to distinguish between primary and secondary reactions and finally lead to finding a target of gravity force.

Articles and reviews will be collected in which mechanisms are unveiled regarding the alterations of proteins caused by the modification of gravity force which subsequently influence physiologic reactions that lead to a modified regulation of cell adhesion and growth under microgravity.

Dr. Johann Bauer
Guest Editor

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Keywords

  • Cell monolayer
  • Organoid formation
  • Adhesion proteins
  • Tight junction

Published Papers (6 papers)

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Research

17 pages, 2549 KiB  
Article
Sperm of Fruit Fly Drosophila melanogaster under Space Flight
by Irina V. Ogneva, Yulia S. Zhdankina and Oleg V. Kotov
Int. J. Mol. Sci. 2022, 23(14), 7498; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147498 - 06 Jul 2022
Cited by 5 | Viewed by 1735
Abstract
Studies of reproductive function under long-term space flight conditions are of interest in planning the exploration of deep space. Motility, including the use of various inhibitors, cellular respiration, and the content of cytoskeletal proteins were studied, assessing the level of expression of the [...] Read more.
Studies of reproductive function under long-term space flight conditions are of interest in planning the exploration of deep space. Motility, including the use of various inhibitors, cellular respiration, and the content of cytoskeletal proteins were studied, assessing the level of expression of the corresponding genes in spermatozoa of Drosophila melanogaster, which were in space flight conditions for 12 days. The experiment was carried out twice on board the Russian Segment of the International Space Station. Sperm motility speed after space flight, and subsequently 16 h after landing, is reduced relative to the control by 20% (p < 0.05). In comparison with the simulation experiment, we showed that this occurs as a result of the action of overloads and readaptation to the Earth’s gravity. At the same time, cellular respiration, the content of proteins of the respiratory chain, and the expression of their genes do not change. We used kinase inhibitor 6-(dimethylamino)purine (6-DMAP) and phosphatase inhibitors; 6-DMAP restored the reduced the speed of spermatozoa in the flight group to that of the control. These results can be useful in developing a strategy for protecting reproductive health during the development of other bodies in the solar system. Full article
(This article belongs to the Special Issue Recent Advances in Microgravity and Cell Adherence)
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15 pages, 4577 KiB  
Article
Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation
by Shuliang Shi, Jing Li, Erzhuo Li, Wenqi Guo, Yao He, Jinpeng Wang, Yao Zhang, Lei Yue and Lijun Wei
Int. J. Mol. Sci. 2022, 23(2), 630; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020630 - 06 Jan 2022
Cited by 3 | Viewed by 2202
Abstract
Space microgravity condition has great physiological influence on astronauts’ health. The interaction of endothelial cells, which control vascular permeability and immune responses, is sensitive to mechanical stress. However, whether microgravity has significant effects on the physiological function of the endothelium has not been [...] Read more.
Space microgravity condition has great physiological influence on astronauts’ health. The interaction of endothelial cells, which control vascular permeability and immune responses, is sensitive to mechanical stress. However, whether microgravity has significant effects on the physiological function of the endothelium has not been investigated. In order to address such a question, a clinostat-based culture model with a HUVEC monolayer being inside the culture vessel under the simulated microgravity (SMG) was established. The transmittance of FITC-tagged dextran was used to estimate the change of integrity of the adherens junction of the HUVEC monolayer. Firstly, we found that the permeability of the HUVEC monolayer was largely increased after SMG treatment. To elucidate the mechanism of the increased permeability of the HUVEC monolayer under SMG, the levels of total expression and activated protein levels of Rap1 and Rap2 in HUVEC cells, which regulate the adherens junction of endothelial cells, were detected by WB and GST pull-down after SMG. As the activation of both Rap1 and Rap2 was significantly decreased under SMG, the expression of Rap1GEF1 (C3G) and Rap1GAP in HUVECs, which regulate the activation of them, was further determined. The results indicate that both C3G and Rap1GAP showed a time-dependent increase with the expression of Rap1GAP being dominant at 48 h after SMG. The down-regulation of the expression of junctional proteins, VE-cadherin and β-catenin, in HUVEC cells was also confirmed by WB and immunofluorescence after SMG. To clarify whether up-regulation of Rap1GAP is necessary for the increased permeability of the HUVEC monolayer after SMG, the expression of Rap1GAP was knocked down by Rap1GAP-shRNA, and the change of permeability of the HUVEC monolayer was detected. The results indicate that knock-down of Rap1GAP reduced SMG-induced leaking of the HUVEC monolayer in a time-dependent manner. In total, our results indicate that the Rap1GAP-Rap signal axis was necessary for the increased permeability of the HUVEC monolayer along with the down-regulation of junctional molecules including VE-cadherin and β-catenin. Full article
(This article belongs to the Special Issue Recent Advances in Microgravity and Cell Adherence)
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11 pages, 2233 KiB  
Article
Simulated Microgravity Inhibits Rodent Dermal Fibroblastic Differentiation of Mesenchymal Stem Cells by Suppressing ERK/β-Catenin Signaling Pathway
by Yansiwei Cheng, Yuhao Zhou, Wenjun Lv, Qing Luo and Guanbin Song
Int. J. Mol. Sci. 2021, 22(19), 10702; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910702 - 02 Oct 2021
Cited by 3 | Viewed by 1763
Abstract
Studies have shown that bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into dermal fibroblasts to participate in skin-repairing. However, at present, little is known about how microgravity affects dermal fibroblastic differentiation of BMSCs in space. The aim of this study was to [...] Read more.
Studies have shown that bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into dermal fibroblasts to participate in skin-repairing. However, at present, little is known about how microgravity affects dermal fibroblastic differentiation of BMSCs in space. The aim of this study was to investigate the effect of simulated microgravity (SMG) on the differentiation of BMSCs into dermal fibroblasts and the related molecular mechanism. Here, using a 2D-clinostat device to simulate microgravity, we found that SMG inhibited the differentiation and suppressed the Wnt/β-catenin signaling and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2). After upregulating the Wnt/β-catenin signaling with lithium chloride (LiCl) treatment, we found that the effect of the differentiation was restored. Moreover, the Wnt/β-catenin signaling was upregulated when phosphorylation of ERK1/2 was activated with tert-Butylhydroquinone (tBHQ) treatment. Taken together, our findings suggest that SMG inhibits dermal fibroblastic differentiation of BMSCs by suppressing ERK/β-catenin signaling pathway, inferring that ERK/β-catenin signaling pathway may act as a potential intervention target for repairing skin injury under microgravity conditions. Full article
(This article belongs to the Special Issue Recent Advances in Microgravity and Cell Adherence)
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11 pages, 1233 KiB  
Article
State of Drosophila melanogaster Ovaries after a Full Cycle of Gametogenesis under Microgravity Modeling: Cellular Respiration and the Content of Cytoskeletal Proteins
by Maria A. Usik, Maria A. Golubkova and Irina V. Ogneva
Int. J. Mol. Sci. 2021, 22(17), 9234; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179234 - 26 Aug 2021
Cited by 4 | Viewed by 1526
Abstract
The effect of weightlessness on gametogenesis and the functional state of female germ cells are still poorly understood. We studied the ovaries of Drosophila melanogaster, the full development cycle of which (from zygote to sexually mature adults) passed under simulated microgravity by [...] Read more.
The effect of weightlessness on gametogenesis and the functional state of female germ cells are still poorly understood. We studied the ovaries of Drosophila melanogaster, the full development cycle of which (from zygote to sexually mature adults) passed under simulated microgravity by a random positioning machine. The rate of cellular respiration was studied by polarography as a parameter reflecting the functional state of mitochondria. The content of cytoskeletal proteins and histones was determined using Western blotting. The relative content of mRNA was determined using qRT-PCR. The results obtained indicated an increase in the rate of cellular respiration under simulated microgravity conditions during the full cycle of gametogenesis in Drosophila melanogaster due to complex I of the respiratory chain. In addition, an increase in the contents of actin cytoskeleton components was observed against the background of an increase in the mRNA content of the cytoskeleton’s encoding genes. Moreover, we observed an increase in the relative content of histone H3 acetylated at Lys9 and Lys27, which may explain the increase in the expression of cytoskeletal genes. In conclusion, the formation of an adaptive pattern of functioning of the Drosophila melanogaster ovaries that developed under simulated microgravity includes structural and functional changes and epigenetic regulation. Full article
(This article belongs to the Special Issue Recent Advances in Microgravity and Cell Adherence)
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12 pages, 2203 KiB  
Article
Simulated Microgravity Effects on Human Adenocarcinoma Alveolar Epithelial Cells: Characterization of Morphological, Functional, and Epigenetic Parameters
by Paolo Degan, Katia Cortese, Alessandra Pulliero, Silvia Bruno, Maria Cristina Gagliani, Matteo Congiu and Alberto Izzotti
Int. J. Mol. Sci. 2021, 22(13), 6951; https://doi.org/10.3390/ijms22136951 - 28 Jun 2021
Cited by 7 | Viewed by 1927
Abstract
Background: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a [...] Read more.
Background: In space, the reduction or loss of the gravity vector greatly affects the interaction between cells. Since the beginning of the space age, microgravity has been identified as an informative tool in biomedicine, including cancer research. The A549 cell line is a hypotriploid human alveolar basal epithelial cell line widely used as a model for lung adenocarcinoma. Microgravity has been reported to interfere with mitochondrial activity, energy metabolism, cell vitality and proliferation, chemosensitivity, invasion and morphology of cells and organelles in various biological systems. Concerning lung cancer, several studies have reported the ability of microgravity to modulate the carcinogenic and metastatic process. To investigate these processes, A549 cells were exposed to simulated microgravity (µG) for different time points. Methods: We performed cell cycle and proliferation assays, ultrastructural analysis of mitochondria architecture, as well as a global analysis of miRNA modulated under µG conditions. Results: The exposure of A549 cells to microgravity is accompanied by the generation of polynucleated cells, cell cycle imbalance, growth inhibition, and gross morphological abnormalities, the most evident are highly damaged mitochondria. Global miRNA analysis defined a pool of miRNAs associated with µG solicitation mainly involved in cell cycle regulation, apoptosis, and stress response. To our knowledge, this is the first global miRNA analysis of A549 exposed to microgravity reported. Despite these results, it is not possible to draw any conclusion concerning the ability of µG to interfere with the cancerogenic or the metastatic processes in A549 cells. Conclusions: Our results provide evidence that mitochondria are strongly sensitive to µG. We suggest that mitochondria damage might in turn trigger miRNA modulation related to cell cycle imbalance. Full article
(This article belongs to the Special Issue Recent Advances in Microgravity and Cell Adherence)
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14 pages, 2790 KiB  
Article
Simulated Microgravity Inhibits the Proliferation of Chang Liver Cells by Attenuation of the Major Cell Cycle Regulators and Cytoskeletal Proteins
by Chi Nguyen Quynh Ho, Minh Thi Tran, Chung Chinh Doan, Son Nghia Hoang, Diem Hong Tran and Long Thanh Le
Int. J. Mol. Sci. 2021, 22(9), 4550; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094550 - 27 Apr 2021
Cited by 7 | Viewed by 3054
Abstract
Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under [...] Read more.
Simulated microgravity (SMG) induced the changes in cell proliferation and cytoskeleton organization, which plays an important factor in various cellular processes. The inhibition in cell cycle progression has been considered to be one of the main causes of proliferation inhibition in cells under SMG, but their mechanisms are still not fully understood. This study aimed to evaluate the effects of SMG on the proliferative ability and cytoskeleton changes of Chang Liver Cells (CCL-13). CCL-13 cells were induced SMG by 3D clinostat for 72 h, while the control group were treated in normal gravity at the same time. The results showed that SMG reduced CCL-13 cell proliferation by an increase in the number of CCL-13 cells in G0/G1 phase. This cell cycle phase arrest of CCL-13 cells was due to a downregulation of cell cycle-related proteins, such as cyclin A1 and A2, cyclin D1, and cyclin-dependent kinase 6 (Cdk6). SMG-exposed CCL-13 cells also exhibited a downregulation of α-tubulin 3 and β-actin which induced the cytoskeleton reorganization. These results suggested that the inhibited proliferation of SMG-exposed CCL-13 cells could be associate with the attenuation of major cell cycle regulators and main cytoskeletal proteins. Full article
(This article belongs to the Special Issue Recent Advances in Microgravity and Cell Adherence)
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