Project description:Identification of gravisensitive miRNAs expression in rat soleus muscle exposed to 7 and 14 days of Hindlimb suspension (HS) simulated microgravity. Microgravity causes muscle atrophy possibly due to muscle wasting overtake regeneration. Results provide insight into the molecular mechanisms regulating muscle atrophy. The expression of 23 out of 174 miRNAs was found to change at least 2-fold of 7 and/or 14 days of TS. By using real-time PCR assays, we verified the microarray data using some of the expected genes.
Project description:In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the astronaut’s health. To gain insight into the role of miRNAs and lncRNAs in response to radiation and microgravity, we analyzed RNA expression profiles in human lymphoblastoid TK6 cells incubated for 24 h in static condition or in rotating condition to stimulate microgravity in space after 2 Gy γ-ray irradiation. Expression of 14 lncRNAs and 17 mRNAs was found to be significantly down-regulated in the simulated microgravity condition. In contrast, irradiation up-regulated the expression of 55 lncRNAs and 56 mRNAs, while only one lncRNA, but no mRNA, was down-regulated. Furthermore, 2 miRNAs, 70 lncRNAs, and 87 mRNAs showed significantly altered expression under simulated microgravity after irradiation, and these changes were independently induced by irradiation and simulated microgravity. Together, our results indicate that simulated microgravity and irradiation additively and independently alter the expression of RNAs and their target genes in human lymphoblastoid cells.
Project description:Identification of gravisensitive miRNAs expression in rat soleus muscle exposed to 7 and 14 days of Hindlimb suspension (HS) simulated microgravity. Microgravity causes muscle atrophy possibly due to muscle wasting overtake regeneration. Results provide insight into the molecular mechanisms regulating muscle atrophy. The expression of 23 out of 174 miRNAs was found to change at least 2-fold of 7 and/or 14 days of TS. By using real-time PCR assays, we verified the microarray data using some of the expected genes. The tissue was collected from Sprague-Dawley rats (8 weeks of age) subjected to 7, 14days of TS. miRNA expression profile was determined in three groups: control (CN), TS for 7 days (TS-7), and TS for 14 days (TS-14).Three miRNA microarray chips were analyzed for mixture of four samples of each of the three groups.
Project description:Microgravity impacts various aspects of human health. Yet the mechanisms of spaceflight-induced health problems are not elucidated. Here we mapped the fusion systemic analysis of the serum metabolome and the circulating microRNAome in a hindlimb unloading rat model to simulate microgravity. The response of serum metabolites and microRNAs to simulated microgravity (SMG) was striking. Integrated pathway analysis of altered serum metabolites and target genes of the significantly altered circulating miRNAs with Integrated Molecular Pathway-Level Analysis (IMPaLA) software was mainly suggestive of modulation of neurofunctional signaling pathways. Particularly, we revealed significantly increased miR-383-5p and decreased aquaporin 4 (AQP4) - in the hippocampus. Utilizing Rrabies Virus Glycoprotein (RVG)-modified exosomes, delivery of miR-383-5p inhibited the expression of AQP4 not only in rat C6 glioma cells in vitro but also in the hippocampus in vivo. Using bioinformatics to map the crosstalk between the circulating metabolome and miRNAome could offer opportunities to understand complex biological systems under microgravity. Our present results suggested that the change of miR-383-5p level and its regulation of target gene AQP4 was one of the potential molecular mechanisms of microgravity induced cognitive impairment in the hippocampus. MiRNA plays an important role during the adaptation to microgavity. In this study, effects of simulated microgravity on circulating microRNA profiles were performed to sreen different expression miRNA and gravity-sensitive miRNAs.
Project description:Identification of gravisensitive gene expression in rat soleus muscle exposed to 7 and 14 days of Hindlimb suspension (HS) simulated microgravity. Microgravity causes muscle atrophy possibly due to muscle wasting overtake regeneration. Results provide insight into the molecular mechanisms regulating muscle atrophy. The expression of 787 (373 upregulated and 414 downregulated) and 923 (491 upregulated and 432 downregulated) genes out of 28000 was altered respectively at least 2-fold of 7 and 14 days TS, which represented 397 (233 upregulated and 164 downregulated) genes of common alteration. By using real-time PCR assays, we verified the microarray data using some of the expected genes.
Project description:Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. Therefore, we used simulated microgravity achieved by growing cells on a 3d clinostat to investigate whether the LINC complex acts to mediate responses to the microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth.