microRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma
microRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma
复制标题
microRNA-21a-5p/PDCD4轴调节间充质干细胞诱导的急性青光眼神经保护
DOI：
10.1093/jmcb/mjx022
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发表时间：
2017-08-01
影响因子：
5.5
通讯作者：
Zhuo, Yehong
中科院分区：
文献类型：
--
作者：
Su, Wenru;Li, Zuohong;Zhuo, Yehong
间充质干细胞（MSCs）已被证明对多种神经系统疾病具有良好的治疗效果；然而，人们对其潜在机制知之甚少。本研究表明，在急性青光眼小鼠模型中，玻璃体内输注MSCs可促进视网膜神经节细胞（RGC）的存活，显著抑制小胶质细胞的激活、TNF-α、IL-1β和活性氧的产生，以及caspase-8和caspase-3的激活。在体外，MSCs抑制caspase-8介导的RGC凋亡和小胶质细胞活化，部分是通过STC1的作用。此外，我们发现microRNA-21a-5p （miR-21）及其靶标PDCD4在体外和体内对STC1的产生和MSCs的神经保护特性至关重要。重要的是，miR-21过表达或PDCD4敲低增强了msc介导的对急性青光眼的神经保护作用。这些数据强调了先前未被认识的神经保护机制，miR-21/PDCD4轴诱导MSCs分泌STC1和其他发挥神经保护作用的因子。因此，调节miR-21/PDCD4轴可能是临床治疗急性青光眼和其他神经系统疾病的一种有希望的策略。
Mesenchymal stem cells (MSCs) have been demonstrated to have promising therapeutic benefits for a variety of neurological diseases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell (RGC) survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microglial activation, partly via the action of stanniocalcin 1 (STC1). Furthermore, we found that microRNA-21a-5p (miR-21) and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR-21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.