Zhang Xiaozhao, Chen Guangjin, He Yan, Tang Qingming, Yin Ying, Jie Ying
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100000, China.
Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China.
Ocul Surf. 2024 Oct;34:430-440. doi: 10.1016/j.jtos.2024.09.008. Epub 2024 Sep 27.
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.
负责产生眼泪和唾液的分泌腺在维持眼部和口腔健康方面发挥着重要作用。腺体分泌的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，这些紊乱背后的调控机制在很大程度上仍未被探索。我们证明，生物钟系统的核心成分BMAL1在调节分泌腺分泌中起关键作用。BMAL1的缺失会在腺泡细胞中诱导空泡化和萎缩表型，随后导致细胞凋亡和腺体功能减退，但不会引发以局部炎症细胞浸润为特征的干燥综合征。从机制上讲，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。在Bmal1基因缺失的大鼠中恢复ITPR2和ITPR3的表达有效地缓解了泪腺和腮腺分泌功能障碍的症状，并显著减轻了节律紊乱大鼠的口干和干眼状况。这些发现突出了BMAL1在调节唾液腺和泪腺分泌中的重要作用，并为治疗与节律紊乱相关的口干和干眼提出了一种新的治疗方法。
