Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication
Influence of high glucose on mesangial cell-derived exosome composition, secretion and cell communication
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DOI：
10.1038/s41598-019-42746-1
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发表时间：
2019-04-18
影响因子：
4.6
通讯作者：
Boim, Mirian Aparecida
中科院分区：
文献类型：
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作者：
Novaes, Antonio da Silva;Borges, Fernanda Teixeira;Boim, Mirian Aparecida
高糖（HG）刺激的肾小球系膜细胞表现出细胞内血管紧张素II（AngII）合成增加，这与AngII靶基因（如促纤维化细胞因子）的上调相关。AngII的胞内分泌效应可由通过外泌体（exosomes，Exos）转移到其他细胞的几种分子介导，外泌体在许多生理和病理条件下的细胞通讯中起关键作用。本研究的目的是研究来源于汞刺激的人肾小球系膜细胞（HG-HMCs）的外泌体对正常未刺激的HMCs的影响。从细胞培养上清液获得来自HMC（C-Exos）和HG-HMC（HG-Exos）的外来体。将HMC与C-Exos或HG-Exos孵育。HG刺激引起Exos数量的变化，但不引起大小的变化。C-Exos和HG-Exos均含有血管紧张素原和肾素，但未检测到血管紧张素转换酶。与C-Exos处理的HMCs相比，HG-Exos处理的HMCs呈现出更高水平的纤维连接蛋白、血管紧张素原、肾素、AT（1）和AT（2）受体，表明HG-Exos改变了正常HMCs的功能。这些结果表明，通过Exos的细胞间通讯可能在糖尿病肾脏的病理生理意义。
Mesangial cells stimulated with high glucose (HG) exhibit increased intracellular angiotensin II (AngII) synthesis that is correlated with the upregulation of AngII target genes, such as profibrotic cytokines. The intracrine effects of AngII can be mediated by several molecules transferred to other cells via exosomes (Exos), which play a key role in cellular communication under many physiological and pathological conditions. The aim of this study was to investigate the effects of exosomes derived from HG-stimulated human mesangial cells (HG-HMCs) on normal unstimulated HMCs. Exosomes from HMCs (C-Exos) and HG-HMCs (HG-Exos) were obtained from cell culture supernatants. HMCs were incubated with C-Exos or HG-Exos. HG stimulus induced a change in the amount but not the size of Exos. Both C-Exos and HG-Exos contained angiotensinogen and renin, but no angiotensin converting enzyme was detected. Compared with HMCs treated with C-Exos, HMCs treated with HG-Exos presented higher levels of fibronectin, angiotensinogen, renin, AT(1) and AT(2) receptors, indicating that HG-Exos modified the function of normal HMCs. These results suggest that the intercellular communication through Exos may have pathophysiological implications in the diabetic kidney.