MicroRNAs Involved in Asthma After Mesenchymal Stem Cells Treatment.
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.
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .|2 Centre for Stem Cell Clinical Research and Application, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Guan-Nan
GN
Tang
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .|2 Centre for Stem Cell Clinical Research and Application, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Cheng-Lin
CL
Li
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .|3 Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China .
Yin
Y
Yao
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .|2 Centre for Stem Cell Clinical Research and Application, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Zhi-Bin
ZB
Xu
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Meng-Xia
MX
Deng
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Shu-Yue
SY
Wang
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Yue-Qi
YQ
Sun
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Jian-Bo
JB
Shi
1 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .|2 Centre for Stem Cell Clinical Research and Application, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China .
Qing-Ling
QL
Fu
D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D001249:Asthma / Q000150:complications / Q000235:genetics* / Q000628:therapy*; D001854:Bone Marrow Cells / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000628:therapy
D016207:Cytokines; D007136:Immunoglobulins; D018836:Inflammation Mediators; D035683:MicroRNAs; D012333:RNA, Messenger; D010047:Ovalbumin; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A