Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.
Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University School of Basic Medical Sciences, Beijing, China.
Oral Dis. 2023 Jul;29(5):2086-2095. doi: 10.1111/odi.14223. Epub 2022 Jun 5.
Tight junctions (TJs) are involved in the regulation of salivary secretion via paracellular pathway. Botulinum toxin type A (BTXA) is widely used for the treatment of hypersecretion diseases such as sialorrhea. This study aimed to investigate the role of TJs in BTXA-inhibited secretion of the submandibular gland (SMG).
BTXA was injected into the SMGs of rats, and the same amount of saline was injected as a control. Western blot, real-time PCR, and immunofluorescence staining were used to detect the expression and distribution of TJ proteins. Paracellular permeability was evaluated using the transepithelial electrical resistance (TER) measurements and fluorescent tracer detection in BTXA-stimulated SMG-C6 cells.
BTXA injection into the SMGs of rats led to increased expression of claudin (Cldn) -1 and Cldn3. Immunofluorescence staining showed no significant changes in the distribution of TJ proteins. In vitro, BTXA increased the TER values and significantly reduced the permeability of fluorescent tracer, suggesting that BTXA decreased the paracellular permeability. The expression levels of Cldn1, Cldn3, and Cldn4 were upregulated after BTXA treatment.
The expression of TJ proteins changed in both animal models and SMG-C6 cells after BTXA treatment, which may contribute to the inhibition of salivary secretion.
紧密连接（TJ）通过细胞旁途径参与唾液分泌的调节。肉毒毒素 A 型（BTXA）广泛用于治疗唾液分泌过多疾病，如流涎症。本研究旨在探讨 TJ 在 BTXA 抑制下颌下腺（SMG）分泌中的作用。
将 BTXA 注射到大鼠的 SMG 中，作为对照注射等量生理盐水。使用 Western blot、实时 PCR 和免疫荧光染色来检测 TJ 蛋白的表达和分布。通过跨上皮电阻（TER）测量和 BTXA 刺激的 SMG-C6 细胞中荧光示踪剂检测来评估细胞旁通透性。
BTXA 注射到大鼠的 SMG 中导致闭合蛋白（Cldn）-1 和 Cldn3 的表达增加。免疫荧光染色显示 TJ 蛋白的分布无明显变化。在体外，BTXA 增加了 TER 值并显著降低了荧光示踪剂的通透性，表明 BTXA 降低了细胞旁通透性。BTXA 处理后 Cldn1、Cldn3 和 Cldn4 的表达水平上调。
BTXA 处理后在动物模型和 SMG-C6 细胞中 TJ 蛋白的表达发生变化，这可能有助于抑制唾液分泌。
