Oestrogen suppresses the adipogenesis of fibro/adipogenic progenitors through reactivating the METTL3–ESR1‐mediated loop in post‐menopausal females
Clinical and Translational Medicine,
Год журнала:
2025,
Номер
15(2)
Опубликована: Янв. 28, 2025
Abstract
Background
Post‐menopausal
women
experience
more
severe
muscular
fatty
infiltration,
though
the
mechanisms
remain
unclear.
The
decline
in
estrogen
levels
is
considered
as
a
critical
physiological
alteration
during
post‐menopause.
Fibro/adipogenic
progenitors
(FAPs)
are
identified
major
contributors
to
infiltration.
This
study
aimed
investigate
detailed
mechanism
underlying
excessive
infiltration
postmenopausal
females.
Methods
Supraspinatus
muscle
samples
were
collected
from
female
patients
with
or
without
menopause,
and
mice
ovariectomy
(OVX),
evaluate
isolated
FAPs.
expressions
of
(estrogen
receptor
1)
ESR1,
methyltransferase‐like
3
(METTL3),
adipogenesis
ability
FAPs
post‐menopausal
OVX
investigated.
RNA
sequencing
(RNA‐Seq)
was
performed
explore
gene
expression
profiles
potential
Pdgfrα‐CreERT2;
Esr1
knockout
(Esr1
KO)
flox/flox
f/f)
mice.
interplay
METTL3‐ESR1
mediated
loop
its
role
regulating
investigated
using
dual
luciferase
reporter
assays,
chromatin
immunoprecipitation
(ChIP),
protein
stability
assays.
effects
supplementation
on
locomotor
function
evaluated
by
immunofluorescent
staining
functional
analysis.
Results
Decreased
ESR1/METTL3
increased
found
female.
METTL3‐mediated
m6A
methylation
promoted
ESR1
mRNA
at
post‐transcriptional
level
modification
stabilizing
mRNA,
while
acted
transcription
factor
that
enhanced
METTL3
turn.
also
suppressed
adipogenic
peroxisome
proliferator‐activated
gamma
(PPARγ),
thereby
inhibiting
Reactivation
alleviated
women,
it
reduced
improved
Conclusion
Excessive
arose
disruption
due
deficiency.
may
serve
novel
intervention
inhibit
FAPs,
ameliorating
improving
Key
points
Oestrogen
insufficiency
disrupted
METTL3ESR1
causing
stabilized
expression,
further
transcription.
inhibited
PPARγ,
Reactivating
via
oestrogen
function.
Язык: Английский
METTL3-dependent m6A modification of GHR mRNA regulates mitochondrial function through mitochondrial biogenesis during myoblast differentiation
Poultry Science,
Год журнала:
2025,
Номер
unknown, С. 105216 - 105216
Опубликована: Апрель 1, 2025
Язык: Английский
Metabolic targeting of regulatory T cells in oral squamous cell carcinoma: new horizons in immunotherapy
Molecular Cancer,
Год журнала:
2024,
Номер
23(1)
Опубликована: Дек. 19, 2024
Oral
squamous
cell
carcinoma
(OSCC)
is
a
prevalent
oral
malignancy,
which
poses
significant
health
risks
with
high
mortality
rate.
Regulatory
T
cells
(Tregs),
characterized
by
their
immunosuppressive
capabilities,
are
intricately
linked
to
OSCC
progression
and
patient
outcomes.
The
metabolic
reprogramming
of
Tregs
within
the
tumor
microenvironment
(TME)
underpins
function,
key
pathways
such
as
tryptophan-kynurenine-aryl
hydrocarbon
receptor,
PI3K-Akt-mTOR
nucleotide
metabolism
significantly
contributing
suppressive
activities.
Targeting
these
offers
novel
therapeutic
approach
reduce
Treg-mediated
immunosuppression
enhance
anti-tumor
responses.
This
review
explores
dependencies
that
sustain
Treg
function
in
OSCC,
highlighting
adaptations
glycolysis,
fatty
acid
oxidation,
amino
signaling
pathway
enable
thrive
challenging
conditions
TME.
Additionally,
discusses
influence
microbiome
on
evaluates
potential
strategies
targeting
pathways.
Despite
promising
interventions,
challenges
selectivity,
toxicity,
heterogeneity,
resistance
mechanisms
remain.
concludes
perspectives
personalized
medicine
integrative
approaches,
emphasizing
need
for
continued
research
translate
findings
into
effective
clinical
applications
treatment.
Язык: Английский