title: NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.
abstract: BACKGROUND
  Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage.
  
  
  METHODS
  Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay.
  
  
  RESULTS
  Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A.
  
  
  CONCLUSIONS
  Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage.
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. Electronic address: tanglili_sjnk@163.com.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Tang
authors.affiliation: Department of Neurology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, 230001, China.
authors.forename: Yuan-bo
authors.initials: YB
authors.lastname: Wu
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
authors.forename: Chuan-qin
authors.initials: CQ
authors.lastname: Fang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qu
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. Electronic address: gzl2013@163.com.
authors.forename: Zong-liang
authors.initials: ZL
authors.lastname: Gao
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D008070:Lipopolysaccharides; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides; C574979:MIRN375 microRNA, rat; D035683:MicroRNAs; C507213:Ndrg2 protein, rat; D009419:Nerve Tissue Proteins
keywords: MiR-375; Microglial M1 polarization; Microvesicles; NDRG2; Neuron damage