Ingles Sue Ann, Wu Liang, Liu Benjamin T, Chen Yibu, Wang Chun-Yeh, Templeman Claire, Brueggmann Doerthe
University of Southern California, Department of Preventive Medicine, Los Angeles, CA 90089, USA; University of Southern California, Department of Obstetrics/Gynecology, Los Angeles, CA 90089, USA.
University of Southern California, Department of Preventive Medicine, Los Angeles, CA 90089, USA.
J Steroid Biochem Mol Biol. 2017 Oct;173:223-227. doi: 10.1016/j.jsbmb.2017.01.011. Epub 2017 Jan 28.
Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)D on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)D, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH)D. Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH)D treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments.
子宫内膜异位症是一种常见的女性生殖系统疾病,其特征是子宫内膜细胞侵入其他器官,常导致盆腔疼痛和不孕。维生素D系统的改变与子宫内膜异位症的发病率和严重程度有关。为了阐明这些关联的潜在机制,我们研究了1,25(OH)D对子宫内膜异位症细胞基因表达的影响。用1,25(OH)D处理源自子宫内膜异位症组织的基质细胞系,并使用RNA测序来鉴定处理细胞和未处理细胞之间差异表达的基因。分别使用Partek Flow和Ingenuity软件套件进行基因本体论和通路分析。我们鉴定出1627个因1,25(OH)D而差异表达的基因(886个下调和741个上调)。只有一个基因CYP24A1强烈上调(369倍)。许多基因强烈下调。1,25(OH)D处理下调了与神经血管生成、细胞运动和侵袭相关的几种遗传通路,包括轴突导向、Rho GDP信号传导和基质金属蛋白酶抑制通路。这些发现支持了维生素D在子宫内膜异位症病理生理学中的作用,并为研究可能的病因和治疗方法提供了新的靶点。