MicroRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma

Wenru Su, Zuohong Li, Yu Jia, Yingting Zhu, Wenjia Cai, Peixing Wan, Yingying Zhang, Song Guo Zheng, Yehong Zhuo

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)289-301
Number of pages13
JournalJournal of Molecular Cell Biology
Volume9
Issue number4
DOIs
StatePublished - Aug 1 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cell Biology

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    Su, W., Li, Z., Jia, Y., Zhu, Y., Cai, W., Wan, P., Zhang, Y., Zheng, S. G., & Zhuo, Y. (2017). MicroRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma. Journal of Molecular Cell Biology, 9(4), 289-301. https://doi.org/10.1093/jmcb/mjx022