Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
Abnormal Expression of DICER1 Leads to Dysregulation of Inflammatory Effectors in Human Synoviocytes
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DICER1 的异常表达导致人类滑膜细胞炎症效应器失调
DOI：
10.1155/2019/6768504
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Lu, Shemin
中科院分区：
文献类型：
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作者：
Jiang, Congshan;Xu, Jing;Lu, Shemin
类风湿性关节炎（RA）和实验性关节炎广泛发生多种microRNA的失调。本研究旨在探讨DICER 1缺陷介导的人滑膜细胞SW 982炎症的可能机制。首先，DICER 1的RNAi导致COX 2、MMP 3和MMP 13蛋白的表达增加，而DICER 1的过表达则降低MMP 13的表达。第二，在来自DICER 1 siRNA处理的细胞的上清液中测定了IL-8的增加和TGF-β1和TIMP 1的减少，而发现DICER 1过表达能够逆转这种作用。免疫途径分析（IPA）软件预测，Dicer 1缺陷诱导的滑膜细胞中细胞因子的失调可能导致滑膜组织中的炎症性疾病。此外，DICER 1缺陷也可以减少凋亡，而DICER 1过表达被发现减少增殖和促进凋亡。此外，DICER 1缺陷可降低多种RA相关miRNA如miR-155的表达。同时，DICER 1过表达可以挽救其低表达水平。miR-155功能的获得或丧失可调节MMP 3和MMP 13的蛋白水平。这些结果表明DICER 1可能通过调控其下游RA相关miRNA发挥作用。我们的数据表明，DICER 1缺陷可导致人滑膜细胞SW 982中的多种促炎事件。该机制的研究可能为调节滑膜细胞的炎症破坏和过度增殖提供可能的靶分子。
Dysregulation of multiple microRNAs widely takes place during rheumatoid arthritis (RA) and experimental arthritides. This study is performed to explore the possible mechanism underlying DICER1 deficiency-mediated inflammation in human synoviocytes SW982. Firstly, RNAi of DICER1 led to increased COX2, MMP3, and MMP13 protein production, while DICER1 overexpression could reduce MMP13 expression. Secondly, the increase of IL-8 and decrease of TGF-β1 and TIMP1 were determined in the supernatant derived from DICER1 siRNA-treated cells, while DICER1 overexpression was found capable to reverse this effect. Ingenuity pathway analysis (IPA) software predicted that the Dicer1 deficiency-induced dysregulated cytokines in synoviocytes could possibly lead to the inflammatory disorders in the synovial tissue. Moreover, DICER1 deficiency could also reduce apoptosis, while DICER1 overexpression was found to decrease the proliferation and enhance apoptosis. In addition, DICER1 deficiency could lower the expression of multiple RA-related miRNAs such as miR-155. Meanwhile, DICER1 overexpression could rescue their low expression levels. And then, gain or loss of miR-155 function could regulate the protein levels of MMP3 and MMP13. These results indicated that DICER1 might play its role through regulating its downstream RA-related miRNAs. Our data demonstrated that DICER1 deficiency could cause multiple proinflammatory events in human synoviocytes SW982. This mechanism study might provide the possible target molecule to modify the inflammatory destruction and overproliferation in synoviocytes.