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Protective effects of microRNA-22-3p against retinal pigment epithelial inflammatory damage by targeting NLRP3 inflammasome.

Journal of cellular physiology (2019-03-31)
Zizhong Hu, Xuehua Lv, Lu Chen, Xunyi Gu, Huiming Qian, Silvia Fransisca, Zhengyu Zhang, Qinghuai Liu, Ping Xie
ABSTRACT

NLRP3, as a crucial inflammasome component, plays important roles in age-related macular degeneration. Though some activators of NLRP3 have been studied, microRNAs (miRNAs) which potentially regulate NLRP3 messenger RNA (mRNA) have not been fully explored in retinal pigment epithelial (RPE) cells and retinopathy. In this study, by miRNA microarray profiling and bioinformatic analysis, we identified that four miRNAs, miR-4286, miR-223-3p, miR-365a, miR-22-3p, may target NLRP3 mRNA in RPE inflammatory damage in vivo. Further, real-time polymerase chain reaction verified that only miR-22-3p was significantly decreased, which was associated with NLRP3 upregulation in blue-light-induced retinopathy. Mechanistically, the dual-fluorescent reporter suggested miR-22-3p directly binds NLRP3 mRNA. Moreover, overexpression of miR-22-3p could significantly reduce whereas inhibition miR-22-3p could increase the mRNA and protein expressions of NLRP3, Caspase-1, and mature IL-1β. Collectively, our results indicate that miR-22-3p plays a suppressive role in RPE damage by targeting NLRP3, which provides new insights into the future intervention to retinopathy.

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Lipopolysaccharides from Escherichia coli O111:B4, γ-irradiated, BioXtra, suitable for cell culture