胰高血糖素样肽1受体在泪腺中的特征和作用:糖尿病性干眼发病机制的新见解。

IF 4.7 2区 医学 Q1 PATHOLOGY
Yan Sun, Yue Zhang, Fan Shi, Ye Li, Congyao Wang, Fenfen Yu, Tingting Chen, Xia Dong, Yuqi Xu, Yu Zhao, Pengxia Wan
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引用次数: 0

摘要

本研究旨在研究胰高血糖素样肽1受体(GLP-1R)在1型糖尿病小鼠泪腺中的表达,并探讨局部应用GLP-1R激动剂(GLP-1RA)对1型糖尿病小鼠泪腺功能的影响。采用酚红线法评估泪液分泌,采用RNA测序(RNA-seq)技术探索高血糖诱导的泪腺损伤相关基因表达谱,并通过组织学分析评估损伤程度。首次发现GLP-1R在泪腺中的表达,并观察到与糖尿病相关的下调趋势。泪腺组织的RNA-seq数据显示,炎症反应通路中差异表达基因(DEGs)富集。组织学分析显示持续高血糖诱导的炎症细胞浸润和泪腺进行性纤维化,导致泪液萎缩和分泌减少。局部应用利拉鲁肽可有效减轻糖尿病小鼠的炎症和纤维化,从而促进泪液的产生。此外,利拉鲁肽局部干预可促进泪腺自噬降解功能。本研究首次验证了GLP-1R在泪腺中的表达及其在糖尿病诱导下的下调;此外,这些研究结果表明,局部使用利拉鲁肽滴眼液(GLP-1RA)可以有效减轻高血糖引起的泪腺损伤,同时促进泪液分泌。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Characterization and Role of Glucagon-Like Peptide 1 Receptor in the Lacrimal Gland: Novel Insights into Diabetic Dry Eye Pathogenesis.

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.

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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
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.
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