Jiao Xinwei, Lu Dingli, Pei Xiaoting, Qi Di, Huang Shenzhen, Song Zongming, Gu Jianqin, Li Zhijie
Henan Eye Institute, Henan Eye Hospital and Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.
Henan Eye Institute, Henan Eye Hospital and Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.
Ocul Surf. 2020 Jul;18(3):438-452. doi: 10.1016/j.jtos.2020.04.013. Epub 2020 May 1.
People with diabetes are at high risk of lacrimal gland dysfunction, but the underlying mechanism is not well understood. In this study, we determined how type 1 diabetes mellitus (T1DM) influences circadian homeostasis of the murine extraorbital lacrimal glands (ELGs).
A T1DM animal model was established by systemic streptozotocin injection in C57BL/6J mice. After 5 weeks, ELGs were collected at 3-h intervals over a 24-h circadian cycle. Total extracted RNA was subjected to high-throughput RNA sequencing, and rhythmic transcriptional data were evaluated using the Jonckheere-Terpstra-Kendall algorithm, Kyoto Encyclopedia of Genes and Genomes pathway analysis, Phase Set Enrichment Analysis, and time series cluster analysis to determine the phase, rhythmicity, and unique signature of the transcripts over temporally coordinated expression. Additionally, mass, cell size, histology, and tear secretion of the ELGs were evaluated.
T1DM globally altered the composition of the ELG transcriptome. Specifically, T1DM significantly reprogrammed the circadian transcriptomic profiles of normal ELGs and reorganized core clock machinery. Unique temporal and clustering enrichment pathways were also rewired by T1DM. Finally, normal daily rhythms of mass, cell size, and tear secretion of mouse ELGs were significantly impaired by streptozotocin-induced diabetes.
T1DM significantly reprograms the diurnal oscillations of the lacrimal glands and impairs their structure and tear secretion. This information may reveal potential targets for improving lacrimal gland dysfunction in patients with diabetes.
糖尿病患者存在泪腺功能障碍的高风险，但其潜在机制尚未完全明确。在本研究中，我们确定了1型糖尿病（T1DM）如何影响小鼠眶外泪腺（ELG）的昼夜节律稳态。
通过对C57BL/6J小鼠全身注射链脲佐菌素建立T1DM动物模型。5周后，在24小时的昼夜周期内每隔3小时收集一次ELG。对提取的总RNA进行高通量RNA测序，并使用琼克海尔-特普斯特拉-肯德尔算法、京都基因与基因组百科全书通路分析、相集富集分析和时间序列聚类分析来评估节律性转录数据，以确定转录本在时间协调表达上的相位、节律性和独特特征。此外，还评估了ELG的质量、细胞大小、组织学和泪液分泌情况。
T1DM全面改变了ELG转录组的组成。具体而言，T1DM显著重新编程了正常ELG的昼夜转录组图谱，并重组了核心生物钟机制。T1DM还重新连接了独特的时间和聚类富集通路。最后，链脲佐菌素诱导的糖尿病显著损害了小鼠ELG的质量、细胞大小和泪液分泌的正常日常节律。
T1DM显著重新编程泪腺的昼夜振荡，并损害其结构和泪液分泌。这些信息可能揭示改善糖尿病患者泪腺功能障碍的潜在靶点。
