2. Academic Validation
  3. BMAL1 deficiency provokes dry mouth and eyes by down-regulating ITPR2/3

BMAL1 deficiency provokes dry mouth and eyes by down-regulating ITPR2/3

  • Ocul Surf. 2024 Sep 27:34:430-440. doi: 10.1016/j.jtos.2024.09.008.
Xiaozhao Zhang 1,  Guangjin Chen 2,  Yan He 1,  Qingming Tang 2,  Ying Yin 3,  Ying Jie 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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. Electronic address: yiny_no1@163.com.
  • 4 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. Electronic address: jie_yingcn@aliyun.com.
PMID: 39343166 DOI: 10.1016/j.jtos.2024.09.008
Abstract

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.

Keywords

BMAL1; Circadian rhythms; ITPR2; ITPR3; Lacrimal glands; Parotid glands.

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