Suppression of high-mobility group box 1 ameliorates xerostomia in a Sjogren syndrome-triggered mouse model
Suppression of high-mobility group box 1 ameliorates xerostomia in a Sjogren syndrome-triggered mouse model
复制标题
抑制高迁移率组盒 1 可改善干燥综合征引发的小鼠模型中的口干症
DOI：
10.1139/cjpp-2019-0337
复制
发表时间：
2020-06-01
影响因子：
2.1
通讯作者：
Sun, Shiren
中科院分区：
文献类型：
--
作者：
Wang, Di;Zhou, Meilan;Sun, Shiren
口干症是一种自觉症状。高迁移率族蛋白 1 (HMGB1) 在许多疾病中促进促炎作用。本研究旨在阐明 HMGB1 在干燥综合征 (SS) 引发的口干症中的作用。使用非肥胖糖尿病（NOD）/Ltj小鼠建立SS触发的口干症模型。结果表明，SS 患者唾液分泌减少，抗干燥综合征 B（抗 SSB）水平升高。 PCR、Western blot 和免疫组织化学实验表明，与对照组相比，SS 中 HMGB1 和水通道蛋白 5 (AQP5) 水平分别升高和降低。当小鼠接受抗 HMGB1 治疗时，由于唾液分泌增加和抗 SSB 水平降低，口干症得到逆转。此外，还发现HMGB1的抑制抑制了Toll样受体4（TLR4）/核因子κB（NF-κB）轴的激活。 TLR4 和 p-I kappa B 水平降低，而 I kappa B α 和 NF-kappa B p65 水平升高。抗 HMGB1 处理后，通过电泳迁移率变动测定 (EMSA)，NF-kappa B p65 结合活性减弱。此外，HMGB1 的抑制促进了 AQP5 的表达。这些发现表明，抑制 HMGB1 通过抑制 HMGB1/TLR4/NF-κ B 信号通路和上调 AQP5 表达来改善 SS 引发的口干症。
Xerostomia is a self-conscious symptom. High-mobility group box 1 (HMGB1) promotes pro-inflammatory effects in many diseases. This study aimed to clarify the role of HMGB1 in Sjogren syndrome (SS)-triggered xerostomia. Nonobese diabetic (NOD)/Ltj mice were used to establish an SS-triggered xerostomia model. The results showed that saliva production was decreased and anti-Sjogren syndrome B (anti-SSB) level was increased in SS. PCR, Western blot, and immunohistochemistry experiments indicated that the HMGB1 and aquaporin 5 (AQP5) levels were enhanced and diminished in SS compared with those in the control, respectively. While the mice were treated with anti-HMGB1, xerostomia was reversed due to the elevated saliva production and reduced anti-SSB level. In addition, it was found that the inhibition of HMGB1 restrained the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappa B) axis activation. The TLR4 and p-I kappa B levels were alleviated, while the I kappa B alpha and NF-kappa B p65 levels were augmented. The NF-kappa B p65 binding activity was attenuated via the electrophoretic mobility shift assay (EMSA) after anti-HMGB1 treatment. Moreover, the repression of HMGB1 facilitated the expression of AQP5. These findings demonstrate that suppression of HMGB1 ameliorates SS-triggered xerostomia via suppressing the HMGB1/TLR4/NF-kappa B signaling pathway and upregulating AQP5 expression.