Protective effects of microRNA-22-3p against retinal pigment epithelial inflammatory damage by targeting NLRP3 inflammasome
Protective effects of microRNA-22-3p against retinal pigment epithelial inflammatory damage by targeting NLRP3 inflammasome
复制标题
microRNA-22-3p靶向NLRP3炎症小体对视网膜色素上皮炎症损伤的保护作用
DOI：
10.1002/jcp.28523
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Xie, Ping
中科院分区：
文献类型：
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作者：
Hu, Zizhong;Lv, Xuehua;Xie, Ping
NLRP 3作为一种重要的炎性物质，在老年性黄斑变性中起重要作用。尽管已经研究了NLRP 3的一些激活剂，但在视网膜色素上皮（RPE）细胞和视网膜病变中尚未充分探索可能调节NLRP 3信使RNA（mRNA）的microRNA（miRNAs）。本研究通过miRNA微阵列分析和生物信息学分析，确定了4种miRNA，miR-4286，miR-22 - 3 - 3 p，miR-365 a，miR-22- 3 p，可能在体内RPE炎症损伤中靶向NLRP 3 mRNA。此外，实时聚合酶链反应证实，只有miR-22- 3 p显著降低，这与蓝光诱导的视网膜病变中的NLRP 3上调相关。从机制上讲，双荧光报告基因表明miR-22- 3 p直接结合NLRP 3 mRNA。此外，过表达miR-22- 3 p可显著降低NLRP 3、Caspase-1和成熟IL-1 β的mRNA和蛋白表达，而抑制miR-22- 3 p则可显著增加NLRP 3、Caspase-1和成熟IL-1 β的mRNA和蛋白表达。总的来说，我们的结果表明miR-22- 3 p通过靶向NLRP 3在RPE损伤中起抑制作用，这为未来视网膜病变的干预提供了新的见解。
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-1 beta. 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.