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MicroRNA-143 and-145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis

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Title
MicroRNA-143 and-145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis
Author(s)
Bong-Ki Hong; Sungyong You; Seung-Ah Yoo; Dohyun Park; Daehee Hwang; Chul-Soo Cho; Wan-Uk Kim
Publication Date
2017-08
Journal
EXPERIMENTAL AND MOLECULAR MEDICINE, v.49, no.8, pp.e363 -
Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
Abstract
Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulin-like growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets. © 2017 KSBMB
URI
http://pr.ibs.re.kr/handle/8788114/3643
DOI
10.1038/emm.2017.108
ISSN
1226-3613
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
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