Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Stomatology, Zhongnan Hospital of Wuhan University, China.
Biochem Pharmacol. 2022 Jul;201:115073. doi: 10.1016/j.bcp.2022.115073. Epub 2022 May 4.
Primary Sjögren's syndrome (pSS) is an autoimmune disease that primarily affects exocrine glands and is characterized by sicca syndrome and systemic manifestation. Mounting evidence indicates that circadian clocks are involved in the onset and progression of autoimmune diseases, including rheumatic arthritis, multiple sclerosis, and systemic lupus erythematosus. However, few studies have reported the expression of clock genes in pSS. There is no ideal therapeutic method for pSS, the management of pSS is mainly palliative, aims to alleviate sicca symptoms. Melatonin is a neuroendocrine hormone mainly secreted by the pineal gland that plays an important role in the maintenance of the circadian rhythm and immunomodulation. Hence, this study aimed to analyse the circadian expression profile of clock genes in pSS, and further evaluate the therapeutic potential of melatonin in pSS. We discovered a distinct clock gene expression profile in the salivary glands of pSS patients and pSS animal model. More importantly, melatonin administration improved the hypofunction of the salivary glands, inhibited inflammatory development, and regulated clock gene expression in animal model of pSS. Our study suggested that the pathogenesis of pSS might correlate with abnormal expression of circadian genes, and that melatonin might be a potential candidate for prevention and treatment of pSS.
原发性干燥综合征（pSS）是一种主要影响外分泌腺的自身免疫性疾病，其特征为干燥综合征和全身表现。越来越多的证据表明，生物钟参与了自身免疫性疾病的发病和进展，包括类风湿关节炎、多发性硬化症和系统性红斑狼疮。然而，很少有研究报道 pSS 中时钟基因的表达。目前尚无治疗 pSS 的理想方法，pSS 的治疗主要是对症治疗，旨在缓解干燥症状。褪黑素是一种主要由松果体分泌的神经内分泌激素，在维持昼夜节律和免疫调节方面发挥着重要作用。因此，本研究旨在分析 pSS 中时钟基因的昼夜表达谱，并进一步评估褪黑素在 pSS 中的治疗潜力。我们发现 pSS 患者和 pSS 动物模型的唾液腺中存在明显的时钟基因表达谱。更重要的是，褪黑素给药改善了唾液腺的功能减退，抑制了炎症的发展，并调节了 pSS 动物模型中时钟基因的表达。我们的研究表明，pSS 的发病机制可能与昼夜基因表达异常有关，褪黑素可能是预防和治疗 pSS 的潜在候选药物。
