Lacrimal gland homeostasis is maintained by the AQP5 pathway by attenuating endoplasmic reticulum stress inflammation in the lacrimal gland of AQP5 knockout mice
Lacrimal gland homeostasis is maintained by the AQP5 pathway by attenuating endoplasmic reticulum stress inflammation in the lacrimal gland of AQP5 knockout mice
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发表时间：
2021-12
期刊：
影响因子：
2.2
通讯作者：
Shaohua Hu;Guohu Di;Xin Cao;Ya-ning Liu;Yihui Wang;Hui Zhao;Dianqiang Wang;Peng Chen
中科院分区：
文献类型：
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作者：
Shaohua Hu;Guohu Di;Xin Cao;Ya-ning Liu;Yihui Wang;Hui Zhao;Dianqiang Wang;Peng Chen
目的AQP5−/−小鼠自发出现干眼症状。本研究的目的是评估由泪腺水通道蛋白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染色和透射电子显微镜分析方法，观察AQP5缺乏对泪腺上皮细胞结构的影响。用荧光素钠染色评价角膜上皮细胞的损伤情况。用实时定量逆转录聚合酶链式反应(qRT-PCR)和免疫印迹法检测细胞内基因和蛋白质的表达谱。槲皮素组小鼠腹腔注射40 mg/kg，对照组小鼠注射等体积二甲基亚砜，连续4周。结果1月龄和6月龄−/−小鼠泪液分泌量较AQP5+/+小鼠下降约50%。透射电子显微镜显示内质网结构受损。AQP5−/−小鼠泪腺内质网应激显著增加。脂滴聚集在基质和腺泡细胞中，并改变了PPARα、Cpt1α和Cpt2在AQP5−/−小鼠体内的脂代谢和基因表达水平。AQP5−/−小鼠泪腺中免疫细胞浸润，趋化因子CXCL1、CXCL2和CCL5基因表达水平升高。槲皮素部分逆转了内质网应激水平、炎症和脂质堆积，并抑制了泪液分泌。结论AQP5缺乏可引起泪腺病理生理改变和功能失代偿。栎素可能通过调节内质网应激水平，改善−/−小鼠泪腺的炎症反应。
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.