Research progress on ferroptosis in Myelodysplastic syndromes
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 28, 2025
Myelodysplastic
syndromes
(MDS)
are
a
group
of
malignancies
characterized
by
clonal
proliferation
hematopoietic
stem
cells,
ineffective
hematopoiesis,
peripheral
cytopenias,
and
high
risk
transformation
to
acute
myeloid
leukemia.
Current
therapeutic
strategies
for
MDS
have
limited
efficacy.
Thus,
identifying
new
targets
prognostic
biomarkers
is
critical
future
research
direction.
Ferroptosis,
type
iron-dependent
programmed
cell
death,
has
become
recent
hotspot
in
the
field
oncology
research.
Recent
results
demonstrated
that
iron
metabolism,
lipid
other
pathways
can
be
targeted
induce
ferroptosis
cells.
In
addition,
ferroptosis-related
genes
significance
prognosis
diagnosis
MDS.
This
article
reviews
current
progress
on
MDS,
including
its
potential
targeting
as
intervention
strategy.
Язык: Английский
Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Окт. 11, 2024
Vascular
calcification
(VC)
arises
from
the
accumulation
of
calcium
salts
in
intimal
or
tunica
media
layer
aorta,
contributing
to
higher
risk
cardiovascular
events
and
mortality.
Despite
this,
mechanisms
driving
VC
remain
incompletely
understood.
We
previously
described
that
nesfatin-1
functioned
as
a
switch
for
vascular
smooth
muscle
cells
(VSMCs)
plasticity
hypertension
neointimal
hyperplasia.
In
this
study,
we
sought
investigate
role
mechanism
VC.
The
expression
was
measured
calcified
VSMCs
aortas,
well
patients.
Loss-
gain-of-function
experiments
were
evaluated
roles
pathogenesis.
transcription
activation
detected
using
mass
spectrometry.
found
levels
both
patients
with
coronary
calcification.
Loss-of-function
revealed
key
regulator
by
facilitating
osteogenic
transformation
VSMCs.
Mechanistically,
promoted
de-ubiquitination
stability
BMP-2
via
inhibiting
E3
ligase
SYTL4,
interaction
potentiated
signaling
induced
phosphorylation
Smad,
followed
HDAC4
nuclear
exclusion.
dissociation
RUNX2
elicited
acetylation
subsequent
translocation,
leading
upregulation
OPN,
critical
player
From
small
library
natural
compounds,
identified
Curculigoside
Chebulagic
acid
reduced
development
binding
nesfatin-1.
Eventually,
designed
spectrometry-based
DNA-protein
screening
identify
STAT3
mediated
context
Overall,
our
study
demonstrates
enhances
thereby
stabilizing
downstream
SMAD1/5/9
HDAC4.
This
cascade
leads
transcriptional
MSX2,
These
insights
position
potential
therapeutic
target
preventing
treating
VC,
advancing
understanding
molecular
underlying
condition.
Язык: Английский
Increased calcification by erythrophagocytosis in aortic valvular interstitial cells
ESC Heart Failure,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 27, 2024
Abstract
Background
Calcific
aortic
valve
disease
(CAVD)
progresses
over
time
to
severe
stenosis
and
eventually
heart
failure.
Recent
evidence
indicates
that
intraleaflet
haemorrhage
(ILH)
strongly
promotes
CAVD
progression.
However,
it
remains
poorly
understood
how
mechanistically
contributes
valvular
calcification.
Method
ILH
was
identified
as
iron
deposition
by
morphological
analysis.
To
elucidate
the
underlying
mechanism,
human
interstitial
cells
(VIC)
were
cultured
in
presence
of
fresh
or
senescent
red
blood
(RBC),
simulating
vivo
conditions.
Result
common
valves
derived
from
patients
with
stenosis.
VIC
undergo
erythrophagocytosis
RBC,
leading
intracellular
accumulation
analogous
observed
following
exposure
extracellular
iron.
The
RBC
significantly
intensified
calcification,
which
mitigated
ferroptosis
inhibition.
Conclusions
Our
results
identify
VIC,
enhanced
calcification
through
ferroptosis.
This
may
be
a
crucial
component
pathophysiological
mechanisms
links
accelerated
Язык: Английский