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促性腺激素释放激素受体刺激引起的肌上皮细胞驱动的腺泡收缩在干燥综合征动物模型的泪腺中受损。

Myoepithelial cell-driven acini contraction in response to oxytocin receptor stimulation is impaired in lacrimal glands of Sjögren's syndrome animal models.

机构信息

Depratement of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.

出版信息

Sci Rep. 2018 Jul 2;8(1):9919. doi: 10.1038/s41598-018-28227-x.

DOI:10.1038/s41598-018-28227-x
PMID:29967327
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6028591/
Abstract

The purpose of the present studies was to investigate the impact of chronic inflammation of the lacrimal gland, as occurs in Sjögren's syndrome, on the morphology and function of myoepithelial cells (MECs). In spite of the importance of MECs for lacrimal gland function, the effect of inflammation on MECs has not been well defined. We studied changes in MEC structure and function in two animal models of aqueous deficient dry eye, NOD and MRL/lpr mice. We found a statistically significant reduction in the size of MECs in diseased compared to control lacrimal glands. We also found that oxytocin receptor was highly expressed in MECs of mouse and human lacrimal glands and that its expression was strongly reduced in diseased glands. Furthermore, we found a significant decrease in the amount of two MEC contractile proteins, α-smooth muscle actin (SMA) and calponin. Finally, oxytocin-mediated contraction was impaired in lacrimal gland acini from diseased glands. We conclude that chronic inflammation of the lacrimal gland leads to a substantial thinning of MECs, down-regulation of contractile proteins and oxytocin receptor expression, and therefore impaired acini contraction. This is the first study highlighting the role of oxytocin mediated MEC contraction on lacrimal gland function.

摘要

本研究旨在探讨泪腺慢性炎症(如干燥综合征中发生的炎症)对肌上皮细胞(MEC)形态和功能的影响。尽管 MEC 对泪腺功能很重要,但炎症对 MEC 的影响尚未得到很好的定义。我们在两种水样液缺乏性干眼症动物模型(NOD 和 MRL/lpr 小鼠)中研究了 MEC 结构和功能的变化。与对照泪腺相比,我们发现患病泪腺中 MEC 的大小有统计学意义的减小。我们还发现,催产素受体在小鼠和人泪腺的 MEC 中高度表达,并且在患病腺体中其表达强烈降低。此外,我们发现两种 MEC 收缩蛋白,α-平滑肌肌动蛋白(SMA)和钙调蛋白的含量显著减少。最后,催产素介导的泪腺腺泡收缩在患病腺体的腺泡中受损。我们得出结论,泪腺的慢性炎症导致 MEC 显著变薄,收缩蛋白和催产素受体表达下调,因此腺泡收缩受损。这是第一项强调催产素介导的 MEC 收缩对泪腺功能作用的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/8a295458def3/41598_2018_28227_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/a7482357b24f/41598_2018_28227_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/19ebacd545e3/41598_2018_28227_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/71cb297fb190/41598_2018_28227_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/8a295458def3/41598_2018_28227_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/a7482357b24f/41598_2018_28227_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/19ebacd545e3/41598_2018_28227_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/71cb297fb190/41598_2018_28227_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/812a/6028591/8a295458def3/41598_2018_28227_Fig6_HTML.jpg

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