基于~1H NMR代谢组学技术探究GRP78蛋白对巨噬细胞极化的干预效应

发布时间：2018-06-27 23:03

本文选题：H + NMR　；参考：《山西大学学报(自然科学版)》2017年01期

【摘要】：巨噬细胞是肿瘤组织中一类十分重要的免疫细胞,它的M2型极化与肿瘤的恶化密切相关。GRP78蛋白作为肿瘤晚期的生物标志物,可以通过影响肿瘤微环境来促进肿瘤恶化,但GRP78对肿瘤组织中巨噬细胞的分化是否具有干预作用依然未知。本研究利用体外纯化的GRP78蛋白来模拟肿瘤细胞分泌的GRP78,用其处理鼠源巨噬细胞RAW264.7,然后通过~1 H NMR技术的代谢组学方法发现经GRP78处理后细胞中有18种代谢产物,培养基中有14种代谢产物的含量发生了明显变化。通过进一步的代谢通路分析,发现在GRP78蛋白处理后,RAW264.7细胞的糖酵解代谢明显减弱,而脂肪酸和氨基酸代谢加强,这与M2型巨噬细胞的代谢类型一致,表明经GRP78处理后,RAW264.7巨噬细胞向M2型分化。这一发现表明肿瘤微环境中GRP78的存在是肿瘤相关巨噬细胞以M2型为主的重要原因,这也为靶向GRP78的肿瘤治疗提供了坚实的理论依据。
[Abstract]:Macrophages are very important immune cells in tumor tissue. The M2 polarization of macrophage is closely related to the deterioration of tumor. As a biomarker of advanced tumor, macrophage can promote the deterioration of tumor by affecting the microenvironment of tumor. However, whether GRP78 can interfere with the differentiation of macrophages in tumor tissues is still unknown. In this study, the purified GRP78 protein was used to mimic the secretion of GRP78 by tumor cells. RAW264.7 was treated with GRP78, and 18 metabolites were found in the cells treated with GRP78 by ~ 1H NMR. The contents of 14 metabolites in culture medium changed obviously. Through further analysis of metabolic pathway, it was found that glycolysis metabolism of RAW264.7 cells decreased significantly after treatment with GRP78 protein, but the metabolism of fatty acids and amino acids was enhanced, which was consistent with the metabolic type of M2 macrophages. The results showed that RAW264.7 macrophages differentiated to M2 type after GRP78 treatment. This finding suggests that the presence of GRP78 in the tumor microenvironment is an important reason for the M2 type of tumor-associated macrophages, which provides a solid theoretical basis for the treatment of tumor targeting GRP78.
【作者单位】：山西大学生物技术研究所化学生物学与分子工程教育部重点实验室;山西大学中医药现代研究中心重点实验室;
【基金】：山西省平台项目(2015091015) 山西省留学基金(2015-7)
【分类号】：R730.51

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