Lacrimal gland homeostasis is maintained by the AQP5 pathway by attenuating endoplasmic reticulum stress inflammation in the lacrimal gland of AQP5 knockout mice.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2021-12-07 eCollection Date: 2021-01-01

Shaohua Hu, Guohu Di, Xin Cao, Yaning Liu, Yihui Wang, Hui Zhao, Dianqiang Wang, Peng Chen

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引用次数: 0

Abstract

Purpose: AQP5^-/- mice spontaneously exhibit dry eye symptoms. The purpose of this study was to assess the endoplasmic reticulum (ER) stress-mediated inflammation generated by a deficiency of aquaporin 5 (AQP5) in the lacrimal gland.

Methods: Hematoxylin and eosin (H&E) staining, Oil Red O staining, and transmission electron microscopy (TEM) analysis were performed to identify structural changes in lacrimal gland epithelial cells because of AQP5 deficiency. Corneal epithelial defects were assessed with sodium fluorescein staining. The expression profiles of mRNA and proteins were determined by quantitative real-time reverse transcription PCR (qRT-PCR) and western blot. Mice in the quercetin group were injected intraperitoneally with 40 mg/kg of quercetin, and the control group was injected with an equal volume of dimethyl sulfoxide (DMSO) for 4 weeks.

Results: Aqueous tear secretion fell at about 50% in 1- and 6-month-old AQP5^-/- mice compared with that of AQP5^+/+ mice. TEM showed that the ER structure was damaged. ER stress was significantly increased in the lacrimal gland of AQP5^-/- mice. Lipid droplets accumulated in the matrix and acinar cells, and changes occurred in the lipid metabolism and gene expression levels for PPARα, CPT1α, and CPT2 in the AQP5^-/- mice. Immune cell infiltration and increases in the gene expression levels of the chemokines CXCL1, CXCL2, and CCL5 were found in the lacrimal gland of AQP5^-/- mice. Quercetin partially reversed ER stress levels, inflammation, and lipid accumulation, and it inhibited tear secretion.

Conclusions: The study data indicated that a deficiency of AQP5 induced pathophysiological changes and functional decompensation of the lacrimal gland. Quercetin may improve the inflammation in the lacrimal glands of AQP5^-/- mice by regulating the ER stress levels.

本刊更多论文

AQP5通路通过减轻AQP5敲除小鼠泪腺内质网应激性炎症来维持泪腺稳态。

目的:AQP5-/-小鼠自发表现干眼症状。本研究的目的是评估泪腺中水通道蛋白5 (AQP5)缺乏引起的内质网(ER)应激介导的炎症。方法:采用苏木精伊红(H&E)染色、油红O染色、透射电镜(TEM)等方法检测AQP5缺乏导致的泪腺上皮细胞结构变化。用荧光素钠染色评估角膜上皮缺损。采用实时定量反转录PCR (qRT-PCR)和western blot检测mRNA和蛋白的表达谱。槲皮素组小鼠腹腔注射槲皮素40 mg/kg，对照组小鼠腹腔注射等体积的二甲亚砜(DMSO)，持续4周。结果:1月龄和6月龄AQP5-/-小鼠与AQP5+/+小鼠相比，泪液分泌下降约50%。透射电镜显示，ER结构被破坏。AQP5-/-小鼠泪腺内质网应激显著升高。AQP5-/-小鼠基质和腺泡细胞中脂滴积累，脂质代谢和PPARα、CPT1α、CPT2基因表达水平发生变化。AQP5-/-小鼠泪腺中免疫细胞浸润，趋化因子CXCL1、CXCL2、CCL5基因表达水平升高。槲皮素部分逆转内质网应激水平、炎症和脂质积累，并抑制泪液分泌。结论:研究数据提示，AQP5缺乏可引起泪腺病理生理变化和功能失代偿。槲皮素可能通过调节内质网应激水平改善AQP5-/-小鼠泪腺炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.