Stem Cell-Derived, microRNA-Carrying Extracellular Vesicles: A Novel Approach to Interfering with Mesangial Cell Collagen Production in a Hyperglycaemic Setting.
Stem Cell-Derived, microRNA-Carrying Extracellular Vesicles: A Novel Approach to Interfering with Mesangial Cell Collagen Production in a Hyperglycaemic Setting.
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干细胞衍生的，携带microRNA的细胞外囊泡：一种在高血糖环境下干扰肾小球细胞胶原蛋白产生的新方法。
DOI：
10.1371/journal.pone.0162417
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Brizzi MF
中科院分区：
文献类型：
--
作者：
Gallo S;Gili M;Lombardo G;Rossetti A;Rosso A;Dentelli P;Togliatto G;Deregibus MC;Taverna D;Camussi G;Brizzi MF
来源于干细胞的细胞外囊泡（EV）被证明是有前途的治疗选择。我们在此研究了来自不同干细胞来源（骨髓（MSC）和人肝（HLSC））的EV对暴露于高脂血症的系膜细胞（MC）的治疗潜力。通过在HG培养的MC中表达显性负性STAT 5构建体（Δ NSTAT 5），我们已经证明miR-21表达受STAT 5控制，其转化为转化生长因子β（TGFβ）表达和胶原蛋白产生。许多方法已被用于显示MSC-和HLSC-衍生的EV两者通过miR-222的转移保护MC免受HG诱导的损伤。这导致STAT 5下调以及MC内miR-21含量、TGFβ表达和基质蛋白合成的减少。此外，我们证明了受体细胞中miR-21和miR-100之间平衡的变化，这是由EV货物的转移引起的，进一步有助于提供有益的效果。有趣的是，这些效应仅在HG培养的细胞中检测到。最后，发现HG降低了核编码的线粒体电子传递链（ETC）组分CoxIV的表达。值得注意的是，EV给药可以挽救HG培养的MC中的CoxIV表达。因此，这些结果表明MSC和HLSC衍生的EV都转移了保护MC免受HG介导的损伤所需的机制。这通过直接干扰破坏性线索的功能性miR-222的水平转移发生。此外，我们的数据表明，EV货物释放到受体细胞中提供了针对有害线粒体信号的额外治疗优势。
Extracellular vesicles (EVs) that are derived from stem cells are proving to be promising therapeutic options. We herein investigate the therapeutic potential of EVs that have been derived from different stem cell sources, bone-marrow (MSC) and human liver (HLSC), on mesangial cells (MCs) exposed to hyperglycaemia. By expressing a dominant negative STAT5 construct (ΔNSTAT5) in HG-cultured MCs, we have demonstrated that miR-21 expression is under the control of STAT5, which translates into Transforming Growth Factor beta (TGFβ) expression and collagen production. A number of approaches have been used to show that both MSC- and HLSC-derived EVs protect MCs from HG-induced damage via the transfer of miR-222. This resulted in STAT5 down-regulation and a decrease in miR-21 content, TGFβ expression and matrix protein synthesis within MCs. Moreover, we demonstrate that changes in the balance between miR-21 and miR-100 in the recipient cell, which are caused by the transfer of EV cargo, further contribute to providing beneficial effects. Interestingly, these effects were only detected in HG-cultured cells. Finally, it was found that HG reduced the expression of the nuclear encoded mitochondrial electron transport chain (ETC) components, CoxIV. It is worth noting that EV administration can rescue CoxIV expression in HG-cultured MCs. These results thus demonstrate that both MSC- and HLSC-derived EVs transfer the machinery needed to preserve MCs from HG-mediated damage. This occurs via the horizontal transfer of functional miR-222 which directly interferes with damaging cues. Moreover, our data indicate that the release of EV cargo into recipient cells provides additional therapeutic advantages against harmful mitochondrial signals.
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影响因子：
3.2
作者：
Maezawa Y;Takemoto M;Yokote K
通讯作者：
Yokote K
影响因子：
3.7
作者：
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通讯作者：
Camussi G
影响因子：
13.6
作者：
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通讯作者：
Bitzer, Markus
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
5.8
作者：
Osipova, Julia;Fischer, Dagmar-Christiane;Haffner, Dieter
通讯作者：
Haffner, Dieter