Secretory glands, responsible for tears and saliva production, play essential roles in maintaining ocular and oral well-being. Disruptions in gland secretion can arise from various factors, including rhythm disturbances associated with sleep disorders. However, the underlying mechanisms governing these disruptions remain largely unexplored. We demonstrate that BMAL1, a core component of the circadian system, plays a critical role in regulating secretory gland secretion. Loss of BMAL1 induces vacuolation and atrophy phenotypes in acinar cells, subsequently leading to cell apoptosis and gland hypofunction, but does not cause Sjogren's syndrome, which is characterized by localized inflammatory cell infiltration. Mechanically, BMAL1 directly modulates the transcription of ITPR2 and ITPR3, thereby altering the secretion of Lactoferrin and Lysozyme. Restoration of ITPR2 and ITPR3 expression in Bmal1-deficient rats effectively alleviated the symptoms of lacrimal and parotid glands secretory dysfunction and significantly reduced dry mouth and dry eye conditions in rhythm-disordered rats. These findings highlight the essential role of BMAL1 in regulating salivary and lacrimal gland secretion and suggest a novel therapeutic approach for treating dry mouth and dry eyes associated with rhythm disorders.

中文翻译：

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BMAL1 缺陷通过下调 ITPR2/3 引起口干和眼干


分泌腺负责泪液和唾液的产生，在维持眼睛和口腔健康方面起着至关重要的作用。腺体分泌紊乱可能由多种因素引起，包括与睡眠障碍相关的节律紊乱。然而，控制这些干扰的潜在机制在很大程度上仍未得到探索。我们证明 BMAL1 是昼夜节律系统的核心组成部分，在调节分泌腺分泌中起关键作用。BMAL1 缺失诱导腺泡细胞空泡化和萎缩表型，随后导致细胞凋亡和腺体功能减退，但不会导致干燥综合征，其特征是局部炎症细胞浸润。在机械上，BMAL1 直接调节 ITPR2 和 ITPR3 的转录，从而改变乳铁蛋白和溶菌酶的分泌。Bmal1 缺陷大鼠 ITPR2 和 ITPR3 表达的恢复有效缓解了节律紊乱大鼠泪腺和腮腺分泌功能障碍的症状，并显著减轻了口干和眼干。这些发现强调了 BMAL1 在调节唾液腺和泪腺分泌中的重要作用，并提出了一种治疗与节律障碍相关的口干和干眼症的新治疗方法。