Yan Sun, Yue Zhang, Fan Shi, Ye Li, Congyao Wang, Fenfen Yu, Tingting Chen, Xia Dong, Yuqi Xu, Yu Zhao, Pengxia Wan
{"title":"Characterization and Role of Glucagon-Like Peptide 1 Receptor in the Lacrimal Gland: Novel Insights into Diabetic Dry Eye Pathogenesis.","authors":"Yan Sun, Yue Zhang, Fan Shi, Ye Li, Congyao Wang, Fenfen Yu, Tingting Chen, Xia Dong, Yuqi Xu, Yu Zhao, Pengxia Wan","doi":"10.1016/j.ajpath.2024.12.003","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to investigate the expression of glucagon-like peptide 1 receptor (GLP-1R) in the lacrimal gland and explore the effects of topical application of GLP-1R agonist on lacrimal gland function in a murine model of type 1 diabetes. Tear secretion was evaluated using phenol red threads, RNA sequencing was used to explore gene expression profiles associated with hyperglycemia-induced lacrimal gland injuries, and histologic analysis was conducted to evaluate the degree of damage. The expression of GLP-1R in the lacrimal gland was first identified, and a down-regulation trend associated with diabetes was observed. RNA-sequencing data from lacrimal gland tissues revealed that differentially expressed genes were enriched in inflammatory response pathways. Histologic analysis demonstrated persistent hyperglycemia-induced infiltration of inflammatory cells and progressive fibrosis in the lacrimal gland, resulting in atrophy and diminished tear secretion. Topical application of liraglutide effectively attenuated inflammation and alleviated fibrosis, thus promoting tear production in diabetic mice. Additionally, local intervention with liraglutide could promote autophagy degradation function in the lacrimal gland. This study represents the first validation of GLP-1R expression in the lacrimal gland and its down-regulation induced by diabetes; furthermore, these findings demonstrate that topical administration of liraglutide eye drops, a GLP-1R agonist, can effectively mitigate hyperglycemia-induced damage in the lacrimal gland while enhancing tear secretion.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2024.12.003","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
This study aimed to investigate the expression of glucagon-like peptide 1 receptor (GLP-1R) in the lacrimal gland and explore the effects of topical application of GLP-1R agonist on lacrimal gland function in a murine model of type 1 diabetes. Tear secretion was evaluated using phenol red threads, RNA sequencing was used to explore gene expression profiles associated with hyperglycemia-induced lacrimal gland injuries, and histologic analysis was conducted to evaluate the degree of damage. The expression of GLP-1R in the lacrimal gland was first identified, and a down-regulation trend associated with diabetes was observed. RNA-sequencing data from lacrimal gland tissues revealed that differentially expressed genes were enriched in inflammatory response pathways. Histologic analysis demonstrated persistent hyperglycemia-induced infiltration of inflammatory cells and progressive fibrosis in the lacrimal gland, resulting in atrophy and diminished tear secretion. Topical application of liraglutide effectively attenuated inflammation and alleviated fibrosis, thus promoting tear production in diabetic mice. Additionally, local intervention with liraglutide could promote autophagy degradation function in the lacrimal gland. This study represents the first validation of GLP-1R expression in the lacrimal gland and its down-regulation induced by diabetes; furthermore, these findings demonstrate that topical administration of liraglutide eye drops, a GLP-1R agonist, can effectively mitigate hyperglycemia-induced damage in the lacrimal gland while enhancing tear secretion.
期刊介绍:
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.