Zhao Jiarui, Jing Jia, Zhao Wei, Li Xinrong, Hou Lixuan, Zheng Chunfeng, Kong Qingfei, Li Wenjin, Yao Xiuhua, Chang Lulu, Li Hulun, Mu Lili, Wang Guangyou, Wang Jinghua
Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin, Heilongjiang 150086, China.
The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar City, Heilongjiang 161000, China.
Int Immunopharmacol. 2020 Feb 25;82:106335. doi: 10.1016/j.intimp.2020.106335.
Osteopontin (OPN) is a multifunctional extracellular matrix phosphoprotein that has a specific and complicated structure, and contributes to numerous physiological and pathological activities. The mechanism of OPN in many diseases has been confirmed; however, the role of OPN in myasthenia gravis (MG) remains unclear. In this study, we recombined rat OPN protein in vitro, and assessed how OPN affects the development of autoimmunity using an experimental autoimmune myasthenia gravis (EAMG) rat model. The results showed that the concentration of OPN in serum was up-regulated. Both mRNA and protein levels in splenocytes increased in the EAMG model. OPN treatment in vitro strongly promoted the differentiation of Th1 cells, and inhibited the differentiation of Treg cells. Intraperitoneal injection of OPN revealed the early incidence of EAMG, and more serious disease. This effect was accompanied by an increased percentage of Th1 cells. In conclusion, OPN likely exacerbates the pathogenesis of EAMG by promoting the differentiation of Th1 cells and inhibiting the differentiation of Treg cells.
骨桥蛋白（OPN）是一种多功能细胞外基质磷蛋白，其结构特异且复杂，并参与多种生理和病理活动。OPN在多种疾病中的作用机制已得到证实；然而，OPN在重症肌无力（MG）中的作用仍不清楚。在本研究中，我们在体外重组大鼠OPN蛋白，并使用实验性自身免疫性重症肌无力（EAMG）大鼠模型评估OPN如何影响自身免疫的发展。结果显示，血清中OPN的浓度上调。EAMG模型中脾细胞的mRNA和蛋白水平均升高。体外给予OPN强烈促进Th1细胞的分化，并抑制调节性T细胞（Treg细胞）的分化。腹腔注射OPN可使EAMG的发病提前，且病情更严重。这种效应伴随着Th1细胞百分比的增加。总之，OPN可能通过促进Th1细胞的分化和抑制Treg细胞的分化而加剧EAMG的发病机制。
