[1]靳鑫,倪田根,王宁,等.PGC-1α通过线粒体介导巨噬细胞极化状态的机制研究[J].第三军医大学学报,2019,41(01):56-62.
 JIN Xin,NI Tiangen,WANG Ning,et al.Mechanism of mitochondria-mediated PGC-1α in macrophage polarization[J].J Third Mil Med Univ,2019,41(01):56-62.
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PGC-1α通过线粒体介导巨噬细胞极化状态的机制研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第01期
页码:
56-62
栏目:
基础医学
出版日期:
2019-01-15

文章信息/Info

Title:
Mechanism of mitochondria-mediated PGC-1α in macrophage polarization
作者:
靳鑫倪田根王宁罗浩军雷悠扬明佳
重庆医科大学附属第二医院乳甲外科
Author(s):
JIN Xin NI Tiangen WANG Ning LUO Haojun LEI Youyang MING Jia

Department of Breast and Thyroid Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

关键词:
乳腺癌肿瘤相关巨噬细胞PGC-1&alpha线粒体功能
Keywords:
breast cancer tumor-associated macrophages PGC-1&alpha mitochondrial function  
分类号:
R392.12; R73362; R737.9
文献标志码:
A
摘要:

目的     探讨通过敲低PGC-1α对肿瘤相关巨噬细胞(tumor associated macrophages,TAMs)极化状态的影响及其机制。方法    以小鼠腹腔巨噬细胞(mouse peritoneal macrophages,PMs)为研究对象,与4T1细胞共培养24 h建立TAMs;shRNA转染构建瞬时低表达PGC-1α的TAMs;Western blot检测TAMs中PGC-1α、TAMs极化指标、TAMs线粒体功能蛋白的蛋白表达;Real-time PCR(qRT-PCR)检测TAMs的mtDNA水平;流式细胞术检测TAMs极化标志物,ROS水平的变化;ATP测定试剂盒检测TAMs中ATP水平的变化。结果    与PMs组比较,TAMs组PGC-1α蛋白表达上调(P<0.05),M2型分泌细胞因子蛋白(TGF-β1、IL-10)表达升高(P<0.05),线粒体功能相关蛋白(NRF-1、TFAM)表达升高(P<0.05),M2型极化标记物(CD206)表达升高(P<0.05),M1型分泌细胞因子蛋白(TNF-α、IL-1β)表达降低(P<0.05);sh-PGC-1α TAMs组较TAMs组发生了相反的变化,即PGC-1α蛋白表达降低(P<0.05),M2型分泌细胞因子蛋白(TGF-β1、IL-10)表达降低(P<0.05),线粒体功能相关蛋白(NRF-1、TFAM)表达降低(P<0.05),M2型极化标记物(CD206)表达降低(P<0.05),M1型分泌细胞因子蛋白(TNF-α、IL-1β)表达升高(P<0.05),M1型极化标记物(CD86)表达升高(P<0.05)。结论   PGC-1α参与了乳腺TAMs向M2极化的过程,其机制可能为癌细胞与TAMs相互作用,增强了TAMs中依赖PGC-1α的线粒体功能,促使细胞向M2分化,并产生M2型细胞因子。

Abstract:

Objective    To investigate the effect of knocking down peroxisome proliferator-activated receptor gamma coactivator -alpha (PGC-1α) on the polarization in tumor-associated macrophages (TAMs). Methods     Mouse peritoneal macrophages (PMs) were co-cultured with mouse mammary tumor cell line 4T1 for 24 h to establish TAMs. shRNAs sequence of PGC-1α was synthesized and transfected to construct TAMs with transient low expression of PGC-1α. Western blotting was used to detect the expression of PGC-1α and mitochondrial function-related proteins. Real-time PCR (qRT-PCR) was employed to measure the mtDNA levels, flow cytometry to detect macrophage polarization markers, reactive oxygen species (ROS) kit to test the generation of ROS, and ATP assay kit to study the ATP level in the TAMs. Results     Compared with PMs, PGC-1α was up-regulated in TAMs (P<0.05), so were the M2-type secreted cytokines (TGF-β1 and IL-10) (P<0.05), mitochondrial function-related proteins [nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM)] (P<0.05), and M2 type polarization marker (CD206) (P<0.05), but the levels of M1 type secreted cytokines (TNF-α and IL-1β) were decreased (P<0.05). sh-PGC-1α transfection led to opposite changes when compared with TAMs (all P<0.05). Conclusion    PGC-1α is involved in the polarization of breast TAMs to M2. The mechanism may be due to the interaction between the tumor cells and TAMs, which enhances the PGC-1α-dependent mitochondrial function in TAMs, promotes cell differentiation to M2, and then produces M2 cytokines.

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更新日期/Last Update: 2019-01-14