Cai Yan, Zhang Yi, Wang Sihan, Changyong E
Department of Oral and Maxillofacial Radiology, Hospital of Stomatology, Jilin University, Changchun, Jilin Province, PR China.
Department of Orthodontics, Hospital of Stomatology, Jilin University, Changchun, Jilin Province, PR China.
Mol Immunol. 2024 Aug;172:68-75. doi: 10.1016/j.molimm.2024.06.002. Epub 2024 Jun 20.
MicroRNA-23b-3p has been demonstrated to act as a safeguard against several autoimmune diseases. However, its role in Sjögren's syndrome (SS) remains unclear.
In order to investigate its role in SS, we administered agomiR-23b-3p or agomiR-NC to non-obese diabetic (NOD) mice via tail vein weekly for 6 weeks. The study examined the saliva flow rate, histological changes in submandibular glands, and levels of autoantibodies. Additionally, the levels of several cytokines, cell apoptosis, and NF-κB signaling were evaluated. The protective effect of miR-23b-3p was confirmed in a cell model.
The results demonstrated that miR-23b-3p overexpression improved salivary flow rates, inhibited lymphocyte infiltration, reduced cytokine levels, and suppressed cell apoptosis in NOD mice. Moreover, NF-κB signaling was inactivated following miR-23b-3p overexpression. In a cellular model of SS, overexpression of miR-23b-3p protected submandibular gland epithelial cells exposed to IFN-γ against apoptosis and inflammation by targeting SOX6.
The study concludes that miR-23b-3p alleviates SS by targeting SOX6 and inhibiting the NF-κB signaling pathway. The miR-23b-3p/SOX6 axis represents a promising avenue for the development of novel therapeutic strategies for SS.
微小RNA-23b-3p已被证明可作为多种自身免疫性疾病的保护因子。然而,其在干燥综合征(SS)中的作用仍不清楚。
为了研究其在SS中的作用,我们通过尾静脉每周给非肥胖糖尿病(NOD)小鼠注射agomiR-23b-3p或agomiR-NC,持续6周。该研究检测了唾液流速、颌下腺的组织学变化以及自身抗体水平。此外,还评估了几种细胞因子的水平、细胞凋亡和NF-κB信号传导。在细胞模型中证实了miR-23b-3p的保护作用。
结果表明,miR-23b-3p过表达可提高NOD小鼠的唾液流速,抑制淋巴细胞浸润,降低细胞因子水平,并抑制细胞凋亡。此外,miR-23b-3p过表达后NF-κB信号传导失活。在SS细胞模型中,miR-23b-3p过表达通过靶向SOX6保护暴露于IFN-γ的颌下腺上皮细胞免受凋亡和炎症。
该研究得出结论,miR-23b-3p通过靶向SOX6并抑制NF-κB信号通路来减轻SS。miR-23b-3p/SOX6轴代表了开发SS新型治疗策略的一个有前景的途径。