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MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.
- Source :
-
Stem cells and development [Stem Cells Dev] 2016 Jun 15; Vol. 25 (12), pp. 883-96. Date of Electronic Publication: 2016 Jun 03. - Publication Year :
- 2016
-
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.
- Subjects :
- Activin Receptors, Type II genetics
Activin Receptors, Type II metabolism
Adult
Animals
Asthma complications
Bone Marrow Cells cytology
Bronchoalveolar Lavage Fluid
Cytokines metabolism
Disease Models, Animal
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Immunoglobulins metabolism
Inflammation complications
Inflammation pathology
Inflammation therapy
Inflammation Mediators metabolism
Mice, Inbred BALB C
MicroRNAs genetics
Ovalbumin
RNA, Messenger genetics
RNA, Messenger metabolism
Respiratory Hypersensitivity genetics
Respiratory Hypersensitivity pathology
Respiratory Hypersensitivity therapy
Asthma genetics
Asthma therapy
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells cytology
MicroRNAs metabolism
Respiratory Hypersensitivity complications
Subjects
Details
- Language :
- English
- ISSN :
- 1557-8534
- Volume :
- 25
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Stem cells and development
- Publication Type :
- Academic Journal
- Accession number :
- 27106170
- Full Text :
- https://doi.org/10.1089/scd.2015.0339