Chen Jing, Zhang Lijie, Lin Jingyu, Wang Zeng, Lin Aiyu
Department of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China.
Department of Neurology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, Fujian, China.
Transl Neurosci. 2023 Oct 17;14(1):20220306. doi: 10.1515/tnsci-2022-0306. eCollection 2023 Jan 1.
Increased B cell activating factor (BAFF) expression in patients with neuromyelitis optica spectrum disorder (NMOSD) is associated with B cell overstimulation, but the underlying mechanism remains unclear. This study aimed to reveal the emerging mechanisms that regulate BAFF expression in the inflammatory process of NMOSD. The results showed that the expression of miR-30b-5p was significantly decreased in NMOSD CD14 monocytes compared with the normal control. Furthermore, we confirmed that metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is an upstream target of miR-30b-5p, and it could act as a ceRNA and absorb miR-30b-5p with reduced expression of miR-30b-5p. The low expression of miR-30b-5p could not bind to BAFF messenger RNA (mRNA), which resulted in the overexpression of both BAFF mRNA and protein expression. Overexpression of BAFF could bind to the corresponding receptors on B cells, which may initiate activation and proliferation of B cells and increase their production of autoantibodies. Therefore, these findings interpreted that excessive MALAT1 expression in NMOSD mononuclear macrophages led to increased BAFF expression by targeting miR-30b-5p, which caused B cell autoimmune reaction and autoantibodies production, aggravated the disease progression of NMOSD.
视神经脊髓炎谱系障碍（NMOSD）患者中B细胞活化因子（BAFF）表达增加与B细胞过度刺激有关，但其潜在机制仍不清楚。本研究旨在揭示在NMOSD炎症过程中调节BAFF表达的新机制。结果显示，与正常对照相比，NMOSD患者CD14单核细胞中miR-30b-5p的表达显著降低。此外，我们证实转移相关肺腺癌转录本1（MALAT1）是miR-30b-5p的上游靶点，它可以作为竞争性内源RNA（ceRNA），在miR-30b-5p表达降低时吸附miR-30b-5p。miR-30b-5p的低表达不能与BAFF信使核糖核酸（mRNA）结合，导致BAFF mRNA和蛋白表达均过度。BAFF的过表达可与B细胞上的相应受体结合，这可能引发B细胞的活化和增殖，并增加其自身抗体的产生。因此，这些发现表明，NMOSD单核巨噬细胞中MALAT1表达过高，通过靶向miR-30b-5p导致BAFF表达增加，进而引起B细胞自身免疫反应和自身抗体产生，加重了NMOSD的疾病进展。
