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 - 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 -