Extracellular vesicles from maternal uterine cells exposed to risk factors cause fetal inflammatory response.
Extracellular vesicles from maternal uterine cells exposed to risk factors cause fetal inflammatory response.
复制标题
暴露在危险因素下的母体子宫细胞外小泡会引起胎儿炎症反应。
DOI：
10.1186/s12964-021-00782-3
复制
发表时间：
2021-10-07
期刊：
影响因子：
--
通讯作者：
Menon R
中科院分区：
文献类型：
--
作者：
Shepherd MC;Radnaa E;Tantengco OA;Kechichian T;Urrabaz-Garza R;Kammala AK;Sheller-Miller S;Menon R
胎儿细胞衍生的外体(细胞外小泡，40-160 nm)是一种通讯渠道，通过诱导母体蜕膜和子宫肌层的炎性变化来发出分娩信号。关于母体细胞衍生的外切体及其在胎儿方面的功能作用，人们知之甚少。这项研究从正常和炎症/氧化应激条件下生长的蜕膜和子宫肌层细胞中分离和鉴定了外体，并确定了它们对胎膜细胞的影响。蜕膜细胞和子宫肌层细胞在标准培养条件下生长(对照组)，或分别在香烟烟雾提取物或肿瘤坏死因子-α作为氧化应激和炎症的代用品暴露48h。从培养液中分离外切体(差示超速离心法和尺寸排除层析)，定量(纳米颗粒跟踪分析)，并根据其大小和形态(冷冻电子显微镜)、标志物(斑点印迹)和货物含量(蛋白质组学和生物信息学分析)进行表征。用109mLExosome处理羊膜上皮细胞和绒毛滋养层细胞24 h，用激光共聚焦显微镜观察胎儿细胞对Exosome的摄取(共聚焦显微镜)和细胞因子反应(IL-6、IL-10和肿瘤坏死因子-α的酶联免疫吸附试验)。蜕膜和子宫肌层细胞的外体都是圆形的，表达运输所需的四环素和内体分选复合体(ESCRT)蛋白标记物。对照细胞外切体和处理细胞外切体的大小和数量没有差异。蛋白质组学分析确定了外切体中的几种常见蛋白质，以及基于细胞类型和处理的独特蛋白质。与对照外体相比，无论是羊膜上皮细胞还是绒毛滋养层细胞，当细胞暴露于经香烟烟雾提取物或肿瘤坏死因子-α处理的蜕膜或子宫肌层细胞的外体时，羊膜上皮细胞和绒毛滋养层细胞上清液中的促炎细胞因子释放均高于对照组。在绒毛滋养层细胞中，蜕膜细胞和子宫肌层细胞的外体均能增强IL-10的抗炎作用。不同的病理生理条件导致母体外切体携带炎症介质，从而导致细胞类型依赖的胎儿炎症反应。视频摘要在线版本包含可在10.1186/s12964-021-00782-3上查阅的补充材料。
Fetal cell-derived exosomes (extracellular vesicles, 40–160 nm) are communication channels that can signal parturition by inducing inflammatory changes in maternal decidua and myometrium. Little is known about maternal cell-derived exosomes and their functional roles on the fetal side. This study isolated and characterized exosomes from decidual and myometrial cells grown under normal and inflammatory/oxidative stress conditions and determined their impact on fetal membrane cells. Decidual and myometrial cells were grown under standard culture conditions (control) or exposed for 48 h to cigarette smoke extract or tumor necrosis factor-α, as proxies for oxidative stress and inflammation, respectively. Exosomes were isolated from media (differential ultra-centrifugation followed by size exclusion chromatography), quantified (nano particle tracking analysis), and characterized in terms of their size and morphology (cryo-electron microscopy), markers (dot blot), and cargo contents (proteomics followed by bioinformatics analysis). Maternal exosomes (109/mL) were used to treat amnion epithelial cells and chorion trophoblast cells for 24 h. The exosome uptake by fetal cells (confocal microscopy) and the cytokine response (enzyme-linked immunosorbent assays for IL-6, IL-10, and TNF-α) was determined. Exosomes from both decidual and myometrial cells were round and expressed tetraspanins and endosomal sorting complexes required for transport (ESCRT) protein markers. The size and quantity was not different between control and treated cell exosomes. Proteomic analysis identified several common proteins in exosomes, as well as unique proteins based on cell type and treatment. Compared to control exosomes, pro-inflammatory cytokine release was higher in both amnion epithelial cell and chorion trophoblast cell media when the cells had been exposed to exosomes from decidual or myometrial cells treated with either cigarette smoke extract or tumor necrosis factor-α. In chorion trophoblast cells, anti-inflammatory IL-10 was increased by exosomes from both decidual and myometrial cells. Various pathophysiological conditions cause maternal exosomes to carry inflammatory mediators that can result in cell type dependent fetal inflammatory response. Video Abstract The online version contains supplementary material available at 10.1186/s12964-021-00782-3.
登录
查看更多内容
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
使用差分超速离心和三种商业试剂对血清外泌体分离的比较研究。
影响因子：
3.7
作者：
Helwa I;Cai J;Drewry MD;Zimmerman A;Dinkins MB;Khaled ML;Seremwe M;Dismuke WM;Bieberich E;Stamer WD;Hamrick MW;Liu Y
通讯作者：
Liu Y
影响因子：
1.8
作者：
Chaiworapongsa, T;Romero, R;Kuivaniemi, H
通讯作者：
Kuivaniemi, H
影响因子：
6
作者：
Menon, Ramkumar;Boldogh, Istvan;Taylor, Robert N.
通讯作者：
Taylor, Robert N.
影响因子：
3.7
作者：
Bhatti, Gaurav;Romero, Roberto;Margolis, Leonid
通讯作者：
Margolis, Leonid