title: Mesenchymal stem cells alleviate experimental rheumatoid arthritis through microRNA-regulated IκB expression.
abstract: Previous studies have demonstrated that mesenchymal stem cell (MSC) transplantation reduces the severity of collagen-induced arthritis (CIA) in mice, which is a model for rheumatoid arthritis (RA) in humans. However, the underlying molecular mechanisms remain ill-defined. Here, we showed that MSC transplantation reduced the activities of NF-κB signaling and decreased microRNA-548e (miR-548e) levels in the joint tissue in CIA-mice, seemingly through activation of transforming growth factor β receptor signaling. Bioinformatics analyses revealed that miR-548e inhibited protein translation of the NF-κB inhibitor, IκB, through binding to the 3'-UTR of the IκB mRNA. MSCs co-transplanted with adeno-associated virus (AAV) carrying miR-548e abolished the therapeutic effects of MSCs on CIA. On the other hand, transplantation of AAV carrying antisense of miR-548e (as-miR-548e) partially mimicked the effects of MSC transplantation on CIA. Together, these data suggest that MSC transplantation may alleviate experimental RA partially through suppressing miR-548e-mediated IκB inhibition.
authors.affiliation: Department of Rheumatology, Shanxi University affiliated the First Hospital, Taiyuan 030001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University affiliated Sixth People's Hospital, South Campus, Shanghai 201400, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Cen
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University affiliated Sixth People's Hospital, South Campus, Shanghai 201400, China.|Department of Nephrology and Rheumatology, Nanfang Medical University affiliated Fengxian Hospital, South Campus, Shanghai 201400, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D020672:I-kappa B Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008811:Mice, Inbred DBA; D035683:MicroRNAs / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference; D013582:Synovial Fluid / Q000166:cytology
chemical_list: D020413:3' Untranslated Regions; D020672:I-kappa B Proteins; C000627150:MIRN-548e microRNA, mouse; D035683:MicroRNAs; D016328:NF-kappa B