METTL3-mediated N6-methyladenosine modification contributes to vascular calcification
Journal of Molecular and Cellular Cardiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 2025
Vascular
calcification
(VC)
is
a
major
adverse
cardiovascular
event
in
chronic
kidney
disease
(CKD)
patients.
N6-methyladenosine
(m6A)
modification
vital
for
many
biological
processes,
but
its
function
and
possible
molecular
mechanisms
VC
are
poorly
understood.
This
study
aimed
to
clarify
the
of
N6-adenosine-methyltransferase-like
3
(METTL3)
VC.
The
results
bioinformatic
analysis
showed
that
METTL3
expression
was
significantly
upregulated
calcified
VSMCs.
finding
corroborated
by
phosphate-induced
VSMCs
models
5/6
nephrectomy-induced
CKD
mouse
models.
Afterward,
Alizarin
Red
S
staining
m6A
dot
blot
demonstrated
overexpression
elevated
levels
encouraged
aortic
rings,
while
knockdown
decreased
inhibited
calcium
deposition
these
experimental
Furthermore,
promoted
via
PTEN/AKT
pathway,
MeRIP
verified
induced
PTEN
mRNA
degradation
modifying
it
with
m6A.
In
addition,
docking
simulations
DARTS
assays
revealed
quercetin
natural
small-molecule
inhibitor
METTL3.
current
investigation
mitigated
reducing
METTL3-dependent
vivo
vitro.
conclusion,
this
unraveled
pathogenic
mechanism
METTL3-mediated
provided
new
insights
establish
as
therapeutic
target
Язык: Английский
Advances in the mechanisms of vascular calcification in chronic kidney disease
Journal of Cellular Physiology,
Год журнала:
2024,
Номер
240(1)
Опубликована: Окт. 11, 2024
Abstract
Vascular
calcification
(VC)
is
common
in
patients
with
advanced
chronic
kidney
disease
(CKD).A
series
of
factors,
such
as
calcium
and
phosphorus
metabolism
disorders,
uremic
toxin
accumulation,
inflammation
oxidative
stress
cellular
senescence,
cause
osteoblast‐like
differentiation
vascular
smooth
muscle
cells,
secretion
extracellular
vesicles,
imbalance
regulatory
which
together
promote
the
development
VC
CKD.
Recent
advances
epigenetics
have
provided
better
tools
for
investigation
etiology
new
approaches
finding
more
accurate
biomarkers.
These
not
only
deepened
our
understanding
pathophysiological
mechanisms
CKD,
but
also
valuable
clues
optimization
clinical
predictors
exploration
potential
therapeutic
targets.
The
aim
this
article
to
provide
a
comprehensive
overview
pathogenesis
CKD
VC,
especially
made
recent
years,
including
various
key
factors
mentioned
above.
Through
analysis,
we
expect
solid
theoretical
foundation
research
direction
future
studies
targeting
specific
establishment
predictive
indicators
strategies.
Язык: Английский
Epigenetic insights into Fragile X Syndrome
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Авг. 16, 2024
Fragile
X
Syndrome
(FXS)
is
a
genetic
neurodevelopmental
disorder
closely
associated
with
intellectual
disability
and
autism
spectrum
disorders.
The
core
of
the
disease
lies
in
abnormal
expansion
CGG
trinucleotide
repeat
sequence
at
5′end
FMR1
gene.
When
repetition
exceeds
200
times,
it
causes
silencing
gene,
leading
to
absence
encoded
mental
retardation
protein
1
(FMRP).
Although
detailed
mechanism
by
which
triggers
gene
yet
be
fully
elucidated,
known
that
this
process
does
not
alter
promoter
region
or
coding
This
discovery
provides
scientific
basis
for
potential
reversal
through
interventional
approaches,
thereby
improving
symptoms
FXS.
Epigenetics,
regulation
depend
on
changes
DNA
sequence,
has
become
new
focus
FXS
research
modulating
expression
reversible
manner.
latest
progress
molecular
genetics
revealed
epigenetics
plays
key
role
pathogenesis
pathophysiological
processes
article
compiles
existing
findings
aim
deepening
understanding
identify
targets
therapeutic
strategies.
Язык: Английский