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MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.

ABSTRACT: Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transplantation of BM-MSCs. We analyzed aberrant miRNAs and key immune regulators using both miRNA and messenger RNA (mRNA) polymerase chain reaction (PCR) arrays. We identified that 296 miRNAs were differently expressed after the induction of asthma and/or the treatment of BM-MSCs, in which 14 miRNAs presented the reverse variation tendency between asthma induction and BM-MSCs transplantation. Mmu-miR-21a-3p, mmu-miR-449c-5p, and mmu-miR-496a-3p were further confirmed to be differently expressed with additional samples and quantitative real-time PCR. With an mRNA PCR array, we identified 19 genes to be involved in the allergy induction and the administration of BM-MSCs. Further target genes analysis revealed that mmu-miR-21a-3p was significantly correlated with the immune regulator activin A receptor, Type IIA (Acvr2a). Mmu-miR-21a-3p had opposite expression with Acvr2a after asthma and BM-MSCs treatment. Acvr2a had binding sites for miR-21a for both mice and human, suggesting that miR-21/Acvr2a axis is conserved between human and mice. Dual-luciferase reporter assay showed that mmu-miR-21a-3p negatively regulated the transcript of Acvr2a. In addition, has-miR-21a inhibitor significantly increased the expression of Acvr2a mRNA in BEAS-2B cells under lipopolysaccharide stimulation. Our results suggest that there were different miRNA and mRNA profiles after asthma induction and BM-MSCs treatment, and the miR-21/Acvr2a axis is an important mechanism for the induction of asthmatic inflammation.

SUBMITTER: Tang GN

PROVIDER: S-EPMC4928133 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.

Tang Guan-Nan GN Li Cheng-Lin CL Yao Yin Y Xu Zhi-Bin ZB Deng Meng-Xia MX Wang Shu-Yue SY Sun Yue-Qi YQ Shi Jian-Bo JB Fu Qing-Ling QL

Stem cells and development 20160603 12

Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transplantation of BM-MSCs. We analyzed aberrant miRNAs and key immune regulators using both miRNA and messenger RNA (mRNA) polymerase chain reaction (PCR) arrays. We identified that 296 m ...[more]

PMID: 27106170

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Project description:In recent years, a large number of differentially expressed genes have been identified in human umbilical cord mesenchymal stem cell (hUMSC) transplants for the treatment of ischemic cerebral infarction. These genes are involved in various biochemical processes, but the role of microRNAs (miRNAs) in this process is still unclear. From the Gene Expression Omnibus (GEO) database, we downloaded two microarray datasets for GSE78731 (messenger RNA (mRNA) profile) and GSE97532 (miRNA profile). The differentially expressed genes screened were compared between the hUMSC group and the middle cerebral artery occlusion group. Gene ontology enrichment and pathway enrichment analyses were subsequently conducted using the online Database for Annotation, Visualization, and Integrated Discovery. Identified genes were applied to perform weighted gene co-suppression analyses, to establish a weighted co-expression network model. Furthermore, the protein-protein interaction network for differentially expressed genes from turquoise modules was built using Cytoscape (version 3.40) and the most highly correlated subnetwork was extracted from the protein-protein interaction network using the MCODE plugin. The predicted target genes for differentially expressed miRNAs were also identified using the online database starBase v3.0. A total of 3698 differentially expressed genes were identified. Gene ontology analysis demonstrated that differentially expressed genes that are related to hUMSC treatment of ischemic cerebral infarction are involved in endocytosis and inflammatory responses. We identified 12 differentially expressed miRNAs in middle cerebral artery occlusion rats after hUMSC treatment, and these differentially expressed miRNAs were mainly involved in signaling in inflammatory pathways, such as in the regulation of neutrophil migration. In conclusion, we have identified a number of differentially expressed genes and differentially expressed mRNAs, miRNA-mRNAs, and signaling pathways involved in the hUMSC treatment of ischemic cerebral infarction. Bioinformatics and interaction analyses can provide novel clues for further research into hUMSC treatment of ischemic cerebral infarction.

Dataset Information

MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.

Publications

MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.

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