The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity.
The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity.
复制标题
由人脂肪组织衍生的间充质干细胞释放的细胞外囊泡的微-RNA货物是通过肥胖来改变的。
DOI：
10.3389/fcell.2021.660851
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Eirin A;Meng Y;Zhu XY;Li Y;Saadiq IM;Jordan KL;Tang H;Lerman A;van Wijnen AJ;Lerman LO
肥胖是一种慢性疾病，会干扰正常的修复过程，包括脂肪间充质干细胞/基质细胞（ASCs）的功能。ASCs产生细胞外囊泡（ev），部分通过其微rna （miRNA）货物激活受体细胞中的修复程序。我们假设肥胖改变了人类asc来源的ev的miRNA表达谱，限制了它们修复受损细胞的能力。在减肥或整容手术期间，分别从肥胖和年龄和性别匹配的非肥胖（瘦）受试者中采集人类ASCs（各n = 5），并分离其ev。通过高通量测序分析，鉴定出差异表达的mirna，并根据细胞成分、分子功能和生物学过程对其基因靶点进行分类。我们在体外评估了人瘦型和肥胖型evs调节损伤的人近端小管上皮（HK2）细胞的炎症、凋亡以及丝裂原活化蛋白激酶（MAPK）和Wnt信号的能力。从瘦型和肥胖型ascs中释放的ev数量相似，但肥胖型ev比瘦型ev少。差异表达分析显示，与瘦型ev相比，肥胖ev中有8个mirna表达上调（fold change < 1.4, p < 0.05）， 75个mirna表达下调（fold change < 0.7, p < 0.05）。在肥胖- ev中上调的mirna参与NFk-B和MAPK信号传导、细胞骨架组织和凋亡的调控，而在肥胖- ev中下调的mirna则涉及细胞周期、血管生成、Wnt和MAPK信号传导。用肥胖- ev治疗损伤的HK2细胞不能减少炎症，并且它们减少凋亡和MAPK信号传导的效果明显低于瘦细胞。肥胖会改变人类asc源性ev的大小和miRNA载货量，以及它们调节受体细胞重要损伤通路的能力。这些观察结果可能指导新策略的发展，以改善肥胖个体的愈合和修复。
Obesity is a chronic disease that interferes with normal repair processes, including adipose mesenchymal stem/stromal cells (ASCs) function. ASCs produce extracellular vesicles (EVs) that activate a repair program in recipient cells partly via their micro-RNA (miRNA) cargo. We hypothesized that obesity alters the miRNA expression profile of human ASC-derived EVs, limiting their capacity to repair injured cells. Human ASCs were harvested from obese and age- and gender-matched non-obese (lean) subjects during bariatric or cosmetic surgeries, respectively (n = 5 each), and their EVs isolated. Following high-throughput sequencing analysis, differentially expressed miRNAs were identified and their gene targets classified based on cellular component, molecular function, and biological process. The capacity of human lean- and obese-EVs to modulate inflammation, apoptosis, as well as mitogen-activated protein kinase (MAPK) and Wnt signaling in injured human proximal tubular epithelial (HK2) cells was evaluated in vitro. The number of EVs released from lean- and obese-ASCs was similar, but obese-EVs were smaller compared to lean-EVs. Differential expression analysis revealed 8 miRNAs upregulated (fold change > 1.4, p < 0.05) and 75 downregulated (fold change < 0.7, p < 0.05) in obese-EVs vs. lean-EVs. miRNAs upregulated in obese-EVs participate in regulation of NFk-B and MAPK signaling, cytoskeleton organization, and apoptosis, whereas those downregulated in obese-EVs are implicated in cell cycle, angiogenesis, and Wnt and MAPK signaling. Treatment of injured HK2 cells with obese-EVs failed to decrease inflammation, and they decreased apoptosis and MAPK signaling significantly less effectively than their lean counterparts. Obesity alters the size and miRNA cargo of human ASC-derived EVs, as well as their ability to modulate important injury pathways in recipient cells. These observations may guide development of novel strategies to improve healing and repair in obese individuals.
登录
查看更多内容
影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
3.7
作者：
Ebrahimi B;Eirin A;Li Z;Zhu XY;Zhang X;Lerman A;Textor SC;Lerman LO
通讯作者：
Lerman LO
影响因子：
4.8
作者：
Farahani, Rahele A.;Farah, Mohamed C.;Eirin, Alfonso
通讯作者：
Eirin, Alfonso
影响因子：
37.8
作者：
Li, MX;Georgakopoulos, D;Wang, YB
通讯作者：
Wang, YB
影响因子：
2.2
作者：
Martins, David;Ani, Chizobam;Norris, AndKeith
通讯作者：
Norris, AndKeith