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2016 ; 19
(7
): 787-93
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Inhibition of microRNA-21 decreases the invasiveness of fibroblast-like
synoviocytes in rheumatoid arthritis via TGF?/Smads signaling pathway
#MMPMID27635204
Xiong G
; Huang Z
; Jiang H
; Pan Z
; Xie J
; Wang S
Iran J Basic Med Sci
2016[Jul]; 19
(7
): 787-93
PMID27635204
show ga
OBJECTIVES: MicroRNA-21 (miR21) is aberrantly elevated in rheumatoid arthritis
(RA) patients, the significance of this microRNA in RA pathogenesis and
treatment, however, has not been investigated. In this study, by using RA-derived
fibroblast-like synoviocyte (FLS) cells as a model, we investigated the effect
and corresponding mechanism of miR21 inhibition on FLSs invasion. MATERIALS AND
METHODS: miR21 expression in synovial tissue and FLSs in RA patients and non-RA
controls were determined by stem-loop RT-PCR. The effect of miR21 on FLSs
viability and invasiveness were evaluated using miR21 inhibition. Cell viability
was evaluated by MTT assay and the expression of genes at mRNA and protein levels
was determined by RT-PCR and Western blot, respectively. RESULTS: Our results
showed that miR21 expression was highly increased in synovial tissue and FLSs in
RA patients. Also, we reported that miR21 inhibitor treatment could significantly
suppress the invasiveness of FLSs without affecting cell viability. The decreased
FLSs invasion by miR21 inhibition was associated with down-regulated expression
of matrix metalloproteinase (MMP)-1, MMP3, and MMP13. Further analysis revealed
that miR21 inhibition could suppress the expression of TGF?1 and Smad4, but
promote that of Smad7. Moreover, suppression of FLS invasion and MMPs expression
by miR21 treatment could be counteracted by additional TGF?1 treatment.
CONCLUSION: Our results indicated that miR21 inhibition can down-regulate the
expression of MMP1, MMP3, and MMP13 and consequently suppress the invasiveness of
FLS, which is achieved through TGF?1/Smad4/7 signaling pathway. The findings of
this study could offer a novel approach for RA treatment.