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2015 ; 10
(3
): e0119912
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Silencing TRPM7 in mouse cortical astrocytes impairs cell proliferation and
migration via ERK and JNK signaling pathways
#MMPMID25799367
Zeng Z
; Leng T
; Feng X
; Sun H
; Inoue K
; Zhu L
; Xiong ZG
PLoS One
2015[]; 10
(3
): e0119912
PMID25799367
show ga
Transient receptor potential melastatin 7 (TRPM7), a non-selective cation
channel, is highly expressed expressed in the brain and plays a critical role in
ischemic neuronal death. Astrocyte, the most abundant cell type in central
nervous system (CNS), exerts many essential functions in the physiological and
pathological conditions. Here we investigated the expression and functions of the
TRPM7 channel in mouse cortical astrocytes. Using reverse transcription (RT)-PCR,
immunostaining, western blot and patch clamp recording, we showed that functional
TRPM7 channel is expressed in cultured mouse cortical astrocytes. Knocking down
TRPM7 with specific siRNA impairs the proliferation and migration of astrocytes
by 40.2% ± 3.9% and 40.1% ± 11.5%, respectively. Consistently, inhibition of
TRPM7 with 2-aminoethoxydiphenyl borate (2-APB) also decreases astrocyte
proliferation and migration by 46.1% ± 2.5% and 64.2% ± 2.4%. MAPKs and Akt
signaling pathways have been shown to be implicated in TRPM7-mediated responses
including cell proliferation and migration. Our data show that suppression of
TRPM7 in astrocytes reduces the phosphorylation of extracellular signal-regulated
kinases (ERK) and c-Jun N-terminal kinases (JNK), but not p38 mitogen-activated
protein kinase and Akt. In addition, TRPM7, as a cation channel, has been
involved in the Ca²? and Mg²? homeostasis in several types of cells. In our
study, we found that silencing TRPM7 decreases the intracellular basal Mg²?
concentration without affecting Ca²? concentration in astrocytes. However, an
addition of Mg²? to the growth medium could not rescue the impaired proliferation
of astrocytes. Together, our data suggest that TRPM7 channel may play a critical
role in the proliferation and migration of astrocytes via the ERK and JNK
pathways.