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Glial cell line‐derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia‐mediated glioma progression
Author(s) -
Huang Yimin,
Zhang Baole,
Haneke Hannah,
Haage Verena,
Lubas Malgorzata,
Yuan Yang,
Xia Pengfei,
Motta Edyta,
Nanvuma Cynthia,
Dzaye Omar,
Hu Feng,
Kettenmann Helmut
Publication year - 2021
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.24768
Subject(s) - glial cell line derived neurotrophic factor , microglia , neurotrophic factors , gdnf family of ligands , microbiology and biotechnology , biology , downregulation and upregulation , tlr2 , cancer research , receptor , chemistry , signal transduction , immunology , inflammation , biochemistry , tlr4 , gene
Glial cell line‐derived neurotrophic factor (GDNF) is released by glioma cells and promotes tumor growth. We have previously found that GDNF released from the tumor cells is a chemoattractant for microglial cells, the immune cells of the central nervous system. Here we show that GDNF increases matrix metalloproteinase (MMP) 9 and MMP14 expression in cultured microglial cells from mixed sexes of neonatal mice. The GDNF‐induced microglial MMP9 and MMP14 upregulation is mediated by GDNF family receptor alpha 1 receptors and dependent on p38 mitogen‐activated protein kinase signaling. In organotypic brain slices, GDNF promotes the growth of glioma and this effect depends on the presence of microglia. We also previously found that MMP9 and MMP14 upregulation can be mediated by Toll‐like receptor (TLR) 2 signaling and here we demonstrate that GDNF increases the expression of TLR1 and TLR2. In conclusion, GDNF promotes the pro‐tumorigenic phenotype of microglia.