TY - JOUR
T1 - MicroRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma
AU - Su, Wenru
AU - Li, Zuohong
AU - Jia, Yu
AU - Zhu, Yingting
AU - Cai, Wenjia
AU - Wan, Peixing
AU - Zhang, Yingying
AU - Zheng, Song Guo
AU - Zhuo, Yehong
N1 - Funding Information:
This study was partially supported by the Natural Science Foundation of China (81470627 and 81670897), key projects from the Natural Science Foundation of Guangdong Province (2014A030308005), and Guangdong Natural Science Funds for Distinguished Young Scholar (2016A030306006).
Publisher Copyright:
© The Author (2017).
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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-a, IL-1ß, 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.
AB - 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-a, IL-1ß, 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.
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U2 - 10.1093/jmcb/mjx022
DO - 10.1093/jmcb/mjx022
M3 - Article
C2 - 28655163
AN - SCOPUS:85031773869
SN - 1674-2788
VL - 9
SP - 289
EP - 301
JO - Journal of Molecular Cell Biology
JF - Journal of Molecular Cell Biology
IS - 4
ER -