Gene/Protein
Disease
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UMLS:C0038454 (
stroke
)
147,016
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Long noncoding RNAs (lncRNA) expression profiles change in the ischemic brain after
stroke
, but their roles in specific cell types after
stroke
have not been studied. We tested the hypothesis that lncRNA modulates brain injury by altering macrophage functions. Using RNA deep sequencing, we identified 73 lncRNAs that were differentially expressed in monocyte-derived macrophages (MoDMs) and microglia-derived macrophages (MiDMs) isolated in the ischemic brain three days after
stroke
. Among these, the lncRNA, GM15628, is highly expressed in pro-inflammatory MoDMs but not in MiDMs, and are functionally related to its neighbor gene,
lymphocyte cytosolic protein 1
(
LCP1
), which plays a role in maintaining cell shape and cell migration. We termed this lncRNA as
Ma
crophage
c
ontained
L
CP1 related
p
ro-
i
nflammatory
l
ncRNA,
Maclpil
. Using cultured macrophages polarized by LPS, M(LPS), we found that downregulation of
Maclpil
in M(LPS) decreased pro-inflammatory gene expression while promoting anti-inflammatory gene expression.
Maclpil
inhibition also reduced the migration and phagocytosis ability of MoDMs by inhibiting
LCP1
. Furthermore, adoptive transfer of
Maclpil
silenced M(LPS), reduced ischemic brain infarction, improved behavioral performance and attenuated penetration of MoDMs in the ischemic hemisphere. We conclude that by blocking macrophage,
Maclpil
protects against acute ischemic
stroke
by inhibiting neuroinflammation.
...
PMID:Silencing the lncRNA
Maclpil
in pro-inflammatory macrophages attenuates acute experimental ischemic stroke via LCP1 in mice. 3089 79