Premium
Α‐synuclein induces microglial cell migration through stimulating HIF‐1α accumulation
Author(s) -
Qiao Hongfei,
He Xijing,
Zhang Qiaojun,
Zhang Ni,
Li Libo,
Hui Yanping,
Li Wenjuan,
Wang Dong,
Wu Zhonghen
Publication year - 2017
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24012
Subject(s) - cell migration , microglia , microbiology and biotechnology , transfection , tlr2 , gene silencing , cell , western blot , downregulation and upregulation , biology , cell culture , chemistry , signal transduction , inflammation , tlr4 , immunology , biochemistry , genetics , gene
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.