title: Α-synuclein induces microglial cell migration through stimulating HIF-1α accumulation.
abstract: Microglial cell migration and infiltration plays a critical role in spinal cord injury after thoracoabdominal aortic surgery. In our previous study, α-synuclein, a presynaptic protein was shown to be released from injured neurons and cause microglial cell activation. Here, we aimed to explore the effect of α-synuclein on microglial cell migration. Primary microglial cells were isolated from Sprague-Dawley rats and then exposed different doses (0.2, 0.4, and 0.6 μM) of α-synuclein oligomers. The mRNA and protein levels of HIF-1α were then analyzed by qRT-PCR and Western blot. Cell migration was examined by a 96-well Boyden chamber. Moreover, toll-like receptor (TLR) 2-expression as well as TLR7/8-expression was inhibited by specific siRNA transfection. HIF-1α was overexpressed by Ad-HIF-1α transfection. In the results, α-synuclein was found to stimulate HIF-1α accumulation in microglial cells in a dose-dependent manner. Silencing HIF-1α expression dampened α-synuclein induced microglial cell migration. Furthermore, blockade of TLR7/8 expression but not TLR2 expression reduced HIF-1α accumulation in microglial cells. In addition, overexpressed HIF-1α, along with Src, prompted caveolin-1 expression and phosphorylation, as well as migration in microglial cells. Α-synuclein acts via TLR7/8 and enhances HIF-1α expression, which might play a regulatory role in microglial cell migration. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Departments of Orthopedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xijing
authors.initials: X
authors.lastname: He
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Li
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Hui
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Departments of Orthopedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Departments of Rehabilitation Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zhonghen
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D001011:Aorta / Q000601:surgery; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000209:etiology; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D014656:Vascular Surgical Procedures / Q000009:adverse effects; D051844:alpha-Synuclein / Q000494:pharmacology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C489639:TLR7 protein, rat; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051844:alpha-Synuclein
keywords: HIF-1α; caveolin-1; microglial cell; spinal cord injury; toll-like receptor 7/8