Glia,
Год журнала:
2022,
Номер
70(11), С. 2079 - 2092
Опубликована: Июль 2, 2022
Abstract
The
pro‐inflammatory
cytokine
interleukin
17
(IL‐17),
that
is
mainly
produced
by
Th17
cells,
has
been
recognized
as
a
key
regulator
in
multiple
sclerosis
(MS)
and
experimental
autoimmune
encephalomyelitis
(EAE).
Reactive
astrocytes
stimulated
proinflammatory
cytokines
including
IL‐17
are
involved
blood
brain
barrier
destruction,
inflammatory
cells
infiltration
spinal
cord
injury.
However,
the
role
of
long
non‐coding
RNAs
(lncRNAs)
induced
pathogenesis
MS
EAE
remains
unknown.
Herein,
we
found
an
IL‐17‐induced
lncRNA
AK018453
promoted
TGF‐β
receptor‐associated
protein
1
(TRAP1)
expression
Smad‐dependent
signaling
mouse
primary
astrocytes.
Knockdown
significantly
suppressed
astrocytosis,
attenuated
phosphorylation
Smad2/3,
reduced
NF‐κB
p65
CBP/P300
binding
to
TRAP1
promoter,
diminished
production
IL‐17‐treated
knockdown
lentiviral
vector
vivo
dramatically
inhibited
inflammation
prevented
mice
from
demyelination
during
progression
EAE.
Together,
these
results
suggest
regulates
IL‐17‐dependent
response
reactive
potentially
promotes
via
TRAP1/Smad
pathway.
Targeting
this
pathway
may
have
therapeutic
potential
for
intervening
demyelinating
diseases.
Journal of Cellular Physiology,
Год журнала:
2019,
Номер
234(12), С. 22153 - 22162
Опубликована: Май 8, 2019
Abstract
Multiple
sclerosis
(MS)
is
a
type
of
inflammatory
and
demyelinating
disorder
the
central
nervous
system
in
which
immune‐mediated
processes
are
elicited
by
secreted
cytokines
from
T
helper
(Th)‐1
Th17
cells.
While
some
protein‐coding
genes
expressed
cell
types
have
established
involvement
MS
disease
progression,
little
understood
about
roles
long
noncoding
RNAs
(lncRNAs)
within
landscape.
LncRNAs,
longer
than
200
nucleotides,
likely
control
gene
expression
function
Th1
cells,
offer
potential
to
act
as
therapeutic
biomarker
candidates
for
MS.
We
identified
lncRNAs
cells
linked
Expression
levels
candidate
were
evaluated
50
patients
25
healthy
controls
using
quantitative
real‐time
polymerase
chain
reaction,
their
correlations
assessed.
LncRNAs
encoded
AC007278.2
IFNG‐AS1‐001
showed
significantly
higher
relapsing
Phase
whereas
IFNG‐AS1‐003
was
elevated
remitting
phase
compared
with
patients.
Collectively,
these
misregulated
may
provide
valuable
tools
understand
relationships
between
MS,
possibly
other
related
disorders.
Neural Regeneration Research,
Год журнала:
2021,
Номер
16(9), С. 1715 - 1715
Опубликована: Янв. 1, 2021
Multiple
sclerosis
is
a
chronic,
inflammatory
and
degenerative
disease
of
the
central
nervous
system
unknown
aetiology
although
well-defined
evidence
supports
an
autoimmune
pathogenesis.
So
far,
exact
mechanisms
leading
to
diseases
are
still
only
partially
understood.
We
know
that
genetic,
epigenetic,
molecular,
cellular
factors
resulting
in
pathogenic
responses
certainly
involved.
Long
non-coding
RNAs
(lncRNAs)
non-protein
coding
transcripts
longer
than
200
nucleotides
play
important
role
both
innate
acquired
immunity,
so
there
great
interest
lncRNAs
involved
diseases.
The
research
on
multiple
has
been
enriched
with
many
studies
molecular
pathogenesis
their
potential
application
as
diagnostic
prognostic
biomarkers.
In
particular,
fields
based
identification
possible
biomarkers
able
predict
onset
disease,
its
activity
degree,
progression
phase
response
disease-modifying
drugs.
Last
but
not
least,
can
provide
new
target
for
therapies,
missing,
cure
sclerosis.
While
our
knowledge
lncRNA
recently
improved,
further
required
better
understand
specific
this
neurological
disease.
review,
we
present
most
recent
characterization
disorder
discussing
clinical
relevance
diagnosis
treatments.
Glia,
Год журнала:
2022,
Номер
70(11), С. 2079 - 2092
Опубликована: Июль 2, 2022
Abstract
The
pro‐inflammatory
cytokine
interleukin
17
(IL‐17),
that
is
mainly
produced
by
Th17
cells,
has
been
recognized
as
a
key
regulator
in
multiple
sclerosis
(MS)
and
experimental
autoimmune
encephalomyelitis
(EAE).
Reactive
astrocytes
stimulated
proinflammatory
cytokines
including
IL‐17
are
involved
blood
brain
barrier
destruction,
inflammatory
cells
infiltration
spinal
cord
injury.
However,
the
role
of
long
non‐coding
RNAs
(lncRNAs)
induced
pathogenesis
MS
EAE
remains
unknown.
Herein,
we
found
an
IL‐17‐induced
lncRNA
AK018453
promoted
TGF‐β
receptor‐associated
protein
1
(TRAP1)
expression
Smad‐dependent
signaling
mouse
primary
astrocytes.
Knockdown
significantly
suppressed
astrocytosis,
attenuated
phosphorylation
Smad2/3,
reduced
NF‐κB
p65
CBP/P300
binding
to
TRAP1
promoter,
diminished
production
IL‐17‐treated
knockdown
lentiviral
vector
vivo
dramatically
inhibited
inflammation
prevented
mice
from
demyelination
during
progression
EAE.
Together,
these
results
suggest
regulates
IL‐17‐dependent
response
reactive
potentially
promotes
via
TRAP1/Smad
pathway.
Targeting
this
pathway
may
have
therapeutic
potential
for
intervening
demyelinating
diseases.
