Zhang Hong-Ju, Wei Qiao-Feng, Wang Shu-Jun, Zhang Hong-Jie, Zhang Xiu-Ying, Geng Qin, Cui Yan-Hui, Wang Xiu-Hua
Department of Rheumatology, ZiBo Central Hospital, Zibo 255036, Shandong Province, PR China.
The Disease Prevention and Control Center of Zibo, Zibo 255000, Shandong Province, PR China.
Int Immunopharmacol. 2017 Sep;50:283-290. doi: 10.1016/j.intimp.2017.06.021. Epub 2017 Jul 18.
Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited. Enforced expression of HOTAIR also led to the upregulation of proliferation-related protein Ki67 and proliferating cell nuclear antigen (PCNA). Moreover, a negative correlation was detected between the expression of HOTAIR and microRNA (miR)-138, and the expression of miR-138 was significantly increased in LPS-induced chondrocytes. The effects of HOTAIR over-expression on the proliferation and inflammation were partly reversed by miR-138 overexpression. Furthermore, the overexpression of HOTAIR significantly inhibited the activation of nuclear transcription factor-κB (NF-κB) in LPS-treated chondrocytes by suppressing p65 to cell nucleus, resulting in the down-regulation of IL-1β and tumor necrosis factor (TNF)-α. In addition, the in vivo experiments exhibited that overexpression of HOTAIR increased cell proliferation and inhibited inflammation in RA rats, which were demonstrated by upregulation of Ki67 and PCNA, reduced CD4IL-17,CD4IL-23 cells, and down-regulation of p-p65, IL-1β and TNF-α. In summary, our study suggests HOTAIR plays a protective role in RA by increasing proliferation rate and inhibiting inflammation, which may be related with the regulation of miR-138 expression and NF-κB signaling pathway. These results suggest that the regulation of HOTAIR may be a promising therapeutic strategy for RA.
类风湿性关节炎（RA）是一种慢性自身免疫介导的炎症性疾病。我们旨在研究长链非编码RNA HOTAIR在脂多糖（LPS）处理的软骨细胞和RA小鼠中的调控作用。我们的结果表明，在LPS处理的软骨细胞中，HOTAIR表达显著降低。然后，通过转染携带编码HOTAIR序列的重组慢病毒，使软骨细胞中HOTAIR过表达。LPS诱导的细胞增殖率降低以及两种炎症因子白细胞介素（IL）-17、IL-23的产生受到明显抑制。HOTAIR的强制表达还导致增殖相关蛋白Ki67和增殖细胞核抗原（PCNA）上调。此外，检测到HOTAIR与微小RNA（miR）-138的表达呈负相关，并且在LPS诱导的软骨细胞中miR-138的表达显著增加。miR-138过表达部分逆转了HOTAIR过表达对增殖和炎症的影响。此外，HOTAIR的过表达通过抑制p65进入细胞核，显著抑制了LPS处理的软骨细胞中核转录因子-κB（NF-κB）的激活，导致IL-1β和肿瘤坏死因子（TNF）-α下调。此外，体内实验表明，HOTAIR过表达增加了RA大鼠的细胞增殖并抑制了炎症，这通过Ki67和PCNA的上调、CD4IL-17、CD4IL-23细胞的减少以及p-p65、IL-1β和TNF-α的下调得以证明。总之，我们的研究表明，HOTAIR通过提高增殖率和抑制炎症在RA中发挥保护作用，这可能与miR-138表达和NF-κB信号通路的调控有关。这些结果表明，HOTAIR的调控可能是一种有前景的RA治疗策略。
