Kasvandik Sergo, Samuel Külli, Peters Maire, Eimre Margus, Peet Nadežda, Roost Anne Mari, Padrik Lee, Paju Kalju, Peil Lauri, Salumets Andres
Proteomics Core Facility, Institute of Technology, University of Tartu , Nooruse 1, Tartu, Estonia.
Competence Centre on Health Technologies , Tiigi 61b, Tartu, Estonia.
J Proteome Res. 2016 Feb 5;15(2):572-84. doi: 10.1021/acs.jproteome.5b00965. Epub 2015 Dec 23.
Endometriosis is a prevalent health condition in women of reproductive age characterized by ectopic growth of endometrial-like tissue in the extrauterine environment. Thorough understanding of the molecular mechanisms underlying the disease is still incomplete. We dissected eutopic and ectopic endometrial primary stromal cell proteomes to a depth of nearly 6900 proteins using quantitative mass spectrometry with a spike-in SILAC standard. Acquired data revealed metabolic reprogramming of ectopic stromal cells with extensive upregulation of glycolysis and downregulation of oxidative respiration, a widespread metabolic phenotype known as the Warburg effect and previously described in many cancers. These changes in metabolism are additionally accompanied by attenuated aerobic respiration of ectopic endometrial stromal cells as measured by live-cell oximetry and by altered mRNA levels of respective enzyme complexes. Our results additionally highlight other molecular changes of ectopic endometriotic stromal cells indicating reduced apoptotic potential, increased cellular invasiveness and adhesiveness, and altered immune function. Altogether, these comprehensive proteomics data refine the current understanding of endometriosis pathogenesis and present new avenues for therapies.
子宫内膜异位症是育龄期女性的一种常见健康状况，其特征是子宫外环境中出现类似子宫内膜组织的异位生长。对该疾病潜在分子机制的全面了解仍不完整。我们使用带有内标SILAC标准的定量质谱分析法，对正常位置和异位的子宫内膜原发性基质细胞蛋白质组进行了深度分析，鉴定出了近6900种蛋白质。获得的数据显示，异位基质细胞发生了代谢重编程，糖酵解广泛上调，氧化呼吸下调，这是一种广泛存在的代谢表型，称为瓦伯格效应，此前在许多癌症中都有描述。通过活细胞血氧测定法以及各酶复合物mRNA水平的改变测量发现，这些代谢变化还伴随着异位子宫内膜基质细胞有氧呼吸减弱。我们的研究结果还突出了异位子宫内膜异位基质细胞的其他分子变化，表明其凋亡潜力降低、细胞侵袭性和黏附性增加以及免疫功能改变。总之，这些全面的蛋白质组学数据完善了目前对子宫内膜异位症发病机制的理解，并为治疗提供了新途径。
