Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells
Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells
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DOI：
10.1002/jcp.26537
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发表时间：
2018-09-01
影响因子：
5.6
通讯作者：
Ciarmela, Pasquapina
中科院分区：
文献类型：
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作者：
Islam, Md Soriful;Castellucci, Clara;Ciarmela, Pasquapina
子宫平滑肌瘤（肌瘤或肌瘤）是绝经前妇女最常见的良性肿瘤，需要新的药物治疗。本研究旨在确定ω-3脂肪酸对脂质分布、膜结构和细胞外基质成分基因表达模式的影响（胶原1A 1、纤连蛋白、多功能蛋白聚糖或激活素A）、机械信号传导（整联蛋白1、FAK和AKAP 13）、固醇调节分子（ABCG 1、ABCA 1、CAV 1和SREBF 2）和线粒体酶（CYP 11 A1）。子宫肌层组织中花生四烯酸含量高于子宫肌瘤组织，而子宫肌瘤组织中亚油酸含量高于子宫肌层组织。用二十碳五烯酸（EPA）或二十二碳六烯酸（DHA）处理原发性子宫肌层和平滑肌瘤细胞，降低了两种细胞类型中单不饱和脂肪酸（MUFA）的含量，增加了多不饱和脂肪酸（PUFA）的含量。子宫肌层和平滑肌瘤细胞膜处于液晶相，但EPA和DHA处理的细胞膜流动性降低。虽然我们发现ECM成分的mRNA表达没有变化，但EPA和DHA处理降低了两种细胞类型中ABCG 1，ABCA 1和AKAP 13的水平。EPA和DHA还降低子宫肌层细胞中FAK和CYP 11 A1的表达。ω-3脂肪酸在平滑肌瘤细胞中重塑膜结构和下调参与机械信号传导和脂质积累的基因表达的能力提供了进一步研究该化合物作为预防和/或治疗选择。
Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin 1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid-crystalline phase, but EPA- and DHA-treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega-3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.