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Stearoyl-CoA 去饱和酶-1 缺乏引起的睑板腺功能障碍导致泪液量和黏蛋白水平代偿性增加。

Compensatory increases in tear volume and mucin levels associated with meibomian gland dysfunction caused by stearoyl-CoA desaturase-1 deficiency.

机构信息

Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Departments of Biochemistry and of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.

出版信息

Sci Rep. 2018 Feb 20;8(1):3358. doi: 10.1038/s41598-018-21542-3.

Abstract

The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated fatty acid synthesis by inserting a cis double bond at the Δ9 position of saturated fatty acids. Disruption of these enzymes has been reported to induce a severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have been associated with dry eye, we analyzed selected eye tissues contributing to tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO), including the lacrimal glands and conjunctiva. Previous histopathological analysis had revealed atrophy and loss of meibomian glands; taken together with the increased goblet cell and MUC5AC expression in the conjunctiva reported here, these findings suggest that the tear volume and mucin levels secreted are enhanced in the absence of lipid secretion as a compensatory mechanism. The expression of lipid metabolism genes in lacrimal glands was decreased in SCD1 KO mice. Thus, these results provide new pathophysiological mechanisms to pursue with regard to meibomian gland dysfunction. In addition, lack of SCD-1 causes a compensatory increase in the tear volume and mucin levels associated with changes in expression of lipid metabolism genes. These results may be useful as a new concept for dry eye treatment strategies.

摘要

硬脂酰辅酶 A 去饱和酶(SCD)家族的酶通过在饱和脂肪酸的 Δ9 位置插入顺式双键来催化单不饱和脂肪酸的合成。据报道,这些酶的破坏会导致严重的干燥皮肤表型。由于睑板腺中的脂质异常与干眼症有关,我们分析了遗传 SCD-1 缺陷型(SCD-1 KO)小鼠中参与泪液体积和成分的选定眼部组织,包括泪腺和结膜。先前的组织病理学分析显示,睑板腺萎缩和丧失;结合这里报道的结膜中杯状细胞和 MUC5AC 表达增加,这些发现表明在缺乏脂质分泌的情况下,作为补偿机制,泪液体积和分泌的粘蛋白水平增加。SCD1 KO 小鼠中泪腺中脂质代谢基因的表达减少。因此,这些结果为研究睑板腺功能障碍提供了新的病理生理学机制。此外,缺乏 SCD-1 会导致与脂质代谢基因表达变化相关的泪液体积和粘蛋白水平的代偿性增加。这些结果可能作为干眼症治疗策略的新概念是有用的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e05/5820245/b1af715b42e9/41598_2018_21542_Fig1_HTML.jpg

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