The reaserch about miR-17 targeting signal transducer and activator of transcription 3 to regulate the proliferation of rheumatoid arthritis synovial fibroblasts and the release of inflammatory factors from rheumatoid arthritis synovial fibroblasts in the pathogenesis of rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective To investigate whether miR-17 plays a role in re-gulation of signal transducer and activator of transcription 3 (STAT3) expression,affecting the proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and the release of inflammatory factors from RASFs.Methods The synovial tissues of rheumatoid arthritis (RA) patients were collected.As a comparison,synovial tissues from osteoarthritis (OA) patients were collected as control,the expression of miR-17,STAT3 were detected.The results were analyzed by Mann-Whitney U test.To analyze the effects of interleukin (IL)-17A treatment on the expression of micro RNA-17 and STAT3,cell proliferation and secretion of IL-6 and IL-8 in RASFs cells.The effects of cell proliferation and secretion of IL-6 and IL-8 were analyzed by cell transfection of micro RNA-17 mimic and siRNA-STAT3.The results about RASFs cells were analyzed by t-testof two independent samples.Results Compared with OA patients,the expression of miR-17 in synovial tissues of RA patients decreased significantly (Mann-Whitney U=6,P＜0.01),while the expression of STAT3 increased obviously (Mann-Whitney U=32,P＜0.01).The expressions of IL-17A,IL-6 and IL-8 in synovial fluid of patients with OA were (53±12),(43±9) and (33±5),respectively,significantly lower than those of patients with RA [(170±30),(222±37) and (156±34),t=18.83,24.28,19.23,P＜0.01].IL-17A treatment significantly lowered the expression of miR-17 [(1.00 ±0.12) vs (0.37±0.04),t=8.63,P＜0.01],while up-regulated the expression of STAT3 [(1.00±0.14) vs (1.92 ±0.23),t =5.92,P＜0.01),promoted the proliferation of RASFs cells,and promoted the release of inflammatory factors IL-6 and IL-8.The results of the double luciferase reporter gene showed that there was a targeting regulation relationship between miR-17 and STAT3.Transfection of miR-17 mimic or siRNA-STAT3 could significantly reduce the expression of STAT3 and p-STAT3 in RASFs cells,along with the inhabitation of cell proliferation [miR-NC vs miR-17 mimic (26.9±2.8) vs (41.5±3.1),t=6.06,P＜0.01;siRNA-NC vs siRNA-STAT3 (23.5±2.4) vs (43.2±3.2),t=8.58,P＜0.01] and reduction of the secretion of inflammatory factors [miR-NC vs miR-17 mimic (110±13) vs (66±9),t=4.88,P＜0.01;siRNA-NC vs siRNA-STAT3 为(117±12) vs (70±6),t=6.10,P＜0.01] and IL-8 [miR-NC vs miR-17 mimic (127±10) vs (72±7),t=8.10,P＜0.01;siRNA-NC vs siRNA-STAT3 (123±11) vs (52±6),t=10.19,P＜0.01].Conclusion Decreased expression of miR-17 may play an important role in enhancing STAT3 expres-sion and promoting the pathogenesis of RA.Overexpression of miR-17 could inhibit STAT3 expression,atten-uate RASFs cell proliferation and inflammatory factor release.