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Study of inhibiting NLRP3-mediated pyroptosis and inflammatory response regulated by microRNA-703 |
Dingqiao Branch, Hangzhou Hospital of Traditional Chinese Medicine, Zhejiang Province, 310044 |
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Abstract To investigate the mechanism progression of the influence of NLRP3-mediated pyroptosis and inflammatory response regulated by microRNA-703 (miR-703) of mice on their endometriosis (EM). Methods: The BABL/C mouse model of endometriosis was established by mouse-to-mouse intraperitoneal implantation. Mice were divided into study group and control group. Immunoblotting and enzyme-linked immunosorbent assay were used to detect the pyroptosis marker proteins (NLRP3, pro-caspase-1, and caspase-1) and the inflammatory factors expressions (IL-1β, IL-18, TNF-α and IL-6). Real-time PCR was used to detect the content of miR-703 in the two groups. Mice that were successfully modeled were intraperitoneally injected with miR-703 NC (EM+NC negative group) and pre-miR-703 (EM+miR-703 group), respectively. The size of the endometriotic tissue and the expressions of pyroptosis marker proteins and inflammatory factors of the mice in the two groups were detected. Results: The protein expressions of NLRP3 and caspase-1 of the mice in the study group were significantly higher than those of the mice in the control group. The levels of inflammatory cytokines, such as IL-1β, IL-18, TNF-α, and IL-6, of the mice in the study group were 1.33±0.11ng/ml, 0.66±0.08ng/ml, 179.69±3.78pg/ml, and 90.375±4.63pg/ml, which were significantly higher than those group (0.30±0.05ng/ml, 0.21±0.03ng/ml, 50.51±2.96pg/ml, and 24.99±1.81pg/ml) of the mice in the control group. The expression of miR-703 (0.52±0.09) in the ectopic tissues of the mice in the study group was significantly lower than that (1.00±0.07) of the mice in the control group (all P<0.05). After transfection of pre-miR-703 in the mice with EM, the EM tissues of the mice in EM+miR-703 group became smaller, the expression of miR-703 of the mice in EM+miR-703 group was significantly higher than that of the mice in EM+NC negative group, the expression of pyroptosis marker protein of the mice in EM+miR-703 group was significantly lower than that of the mice in EM+NC negative group, and the levels of inflammatory factors of the mice in EM+miR-703 group were significantly lower than those of the mice in EM+NC negative group (all P<0.05). Conclusion: MiR-703 may improve endometriosis symptoms by inhibiting NLRP3-mediated pyroptosis and inflammatory response.
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