PubMed,
Год журнала:
2023,
Номер
25(6), С. 391 - 398
Опубликована: Июнь 28, 2023
Peroxiredoxin-3
(Prx-3)
is
widely
acknowledged
as
an
antioxidant
that
protects
against
mitochondrial
reactive
oxygen
species.
Nonetheless,
its
role
in
cardiac
fibrosis
has
not
been
elucidated.
We
aim
to
explore
the
and
mechanism
of
Prx-3
fibrosis.In
this
experimental
study,
mice
received
subcutaneous
injections
isoproterenol
(ISO)
for
14
consecutive
days
(10
mg/kg/d
three
days,
followed
by
5
11
days)
establish
a
model.
The
were
subsequently
injected
with
adenovirus-Prx-3
(ad-Prx-3)
enable
overexpression.
Echocardiography
was
used
evaluate
function.
Mice
heart
fibroblasts
isolated
stimulated
transforming
growth
factor
β1
(TGFβ1)
induce
vitro.
Cells
also
transfected
ad-Prx-3
overexpression
Prx-3.Echocardiographic
diameters
markers
indicated
could
inhibit
ISO-induced
dysfunction
fibrosis.
Fibroblasts
exhibited
reduced
activation,
proliferation,
collagen
transcription.
found
expression
NADPH
oxidase
4
(NOX4)
P38
levels.
After
treatment
inhibitor,
overexpression-induced
anti-fibrosis
effect
mitigated.Prx-3
protect
inhibiting
NOX4-P38
pathway.
Journal of Molecular Medicine,
Год журнала:
2024,
Номер
102(6), С. 733 - 750
Опубликована: Апрель 11, 2024
Abstract
The
accumulation
of
senescent
cells
within
tissues
is
a
hallmark
the
aging
process.
Senescent
are
also
commonly
present
in
many
age-related
diseases
and
cancer
microenvironment.
escape
abnormal
from
immune
surveillance
indicates
that
there
some
defect
function
cytotoxic
cells,
e.g.,
CD8
+
T
natural
killer
(NK)
cells.
Recent
studies
have
revealed
expression
programmed
death-ligand
1
(PD-L1)
protein
abundantly
increased
An
increase
amount
PD-L1
protects
clearance
by
PD-1
checkpoint
receptor
In
fact,
activation
suppresses
properties
NK
promoting
state
immunosenescence.
inhibitory
PD-1/PD-L1
pathway
acts
cooperation
with
immunosuppressive
cells;
for
example,
can
enhance
differentiation
regulatory
(Treg),
myeloid-derived
suppressor
(MDSC),
M2
macrophages,
whereas
cytokines
secreted
stimulate
protein.
Interestingly,
signaling
pathways
known
to
promote
cellular
senescence
process
crucial
stimulators
protein,
epigenetic
regulation,
inflammatory
mediators,
mTOR-related
signaling,
cGAS-STING
pathway,
AhR
signaling.
It
seems
axis
has
role
thus
it
promotes
tissues.
Thus,
blockade
might
be
potential
anti-aging
senolytic
therapy.
Key
messages
accumulate
during
diseases.
able
Expression
markedly
increases
Age-related
stimulates
Inhibitory
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Фев. 5, 2024
Abstract
Cellular
senescence
represents
an
irreversible
state
of
cell-cycle
arrest
during
which
cells
secrete
senescence-associated
secretory
phenotypes,
including
inflammatory
factors
and
chemokines.
Additionally,
these
exhibit
apoptotic
resistance
phenotype.
serves
a
pivotal
role
not
only
in
embryonic
development,
tissue
regeneration,
tumor
suppression
but
also
the
pathogenesis
age-related
degenerative
diseases,
malignancies,
metabolic
kidney
diseases.
The
renal
tubular
epithelial
(RTEC)
constitutes
critical
cellular
event
progression
acute
injury
(AKI).
RTEC
inhibits
regeneration
repair
processes
and,
concurrently,
promotes
transition
AKI
to
chronic
disease
via
mechanisms
underlying
are
multifaceted
include
telomere
shortening
or
damage,
DNA
mitochondrial
autophagy
deficiency,
disorders,
endoplasmic
reticulum
stress,
epigenetic
regulation.
Strategies
aimed
at
inhibiting
senescence,
targeting
clearance
senescent
RTEC,
promoting
apoptosis
hold
promise
for
enhancing
prognosis
AKI.
This
review
primarily
focuses
on
characteristics
impact
intervening
AKI,
aiming
provide
foundation
understanding
providing
potentially
effective
approaches
treatment.
Cardiovascular Research,
Год журнала:
2024,
Номер
120(6), С. 567 - 580
Опубликована: Фев. 23, 2024
Abstract
Hypertension
is
a
major
cause
of
cardiovascular
diseases
such
as
myocardial
infarction
and
stroke.
Cardiovascular
fibrosis
occurs
with
hypertension
contributes
to
vascular
resistance,
aortic
stiffness,
cardiac
hypertrophy.
However,
the
molecular
mechanisms
leading
fibroblast
activation
in
remain
largely
unknown.
There
are
two
types
fibrosis:
replacement
reactive
fibrosis.
Replacement
response
loss
viable
tissue
form
scar.
Reactive
an
increase
mechanical
neurohormonal
stress.
Although
both
considered
adaptive
processes,
they
become
maladaptive
when
too
large,
or
stress
persists.
Myofibroblasts
represent
subpopulation
activated
fibroblasts
that
have
gained
contractile
function
promote
wound
healing.
Therefore,
myofibroblasts
critical
cell
type
promotes
were
recognized
participating
fibrosis,
recent
experimental
evidence
indicated
there
distinct
populations
Accordingly,
we
will
discuss
updated
definition
subpopulations,
regulatory
mechanisms,
their
potential
roles
pathophysiology
utilizing
new
knowledge
from
various
lineage
tracing
single-cell
RNA
sequencing
studies.
Among
highlight
novel
matrifibrocytes
immune
fibrocytes
including
models
hypertension,
pressure
overload,
infarction,
atherosclerosis,
aneurysm,
nephrosclerosis.
Exploration
into
involved
differentiation
those
subpopulations
may
lead
treatments
for
end-organ
damage
associated
other
diseases.
Journal of Advanced Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
After
significant
advancements
in
tumor
treatment,
personalized
cell
therapy
based
on
chimeric
antigen
receptors
(CAR)
holds
promise
for
transforming
the
management
of
various
diseases.
CAR-T
therapy,
first
approved
CAR
product,
has
demonstrated
therapeutic
potential
treating
infectious
diseases,
autoimmune
disorders,
and
fibrosis.
CAR-macrophages
(CAR-Ms)
are
emerging
as
a
promising
approach
immune
particularly
solid
highlighting
feasibility
using
macrophages
to
eliminate
pathogens
abnormal
cells.
European Journal of Pharmacology,
Год журнала:
2024,
Номер
975, С. 176632 - 176632
Опубликована: Май 6, 2024
Myocardial
fibrosis
(MF)
is
a
pivotal
pathological
process
implicated
in
various
cardiovascular
diseases,
particularly
heart
failure.
Astragaloside
IV
(AS-IV),
natural
compound
derived
from
Astragalus
membranaceus,
possesses
potent
cardioprotective
properties.
However,
the
precise
molecular
mechanisms
underlying
its
anti-MF
effects,
relation
to
senescence,
remain
elusive.
Thus,
this
study
aimed
investigate
therapeutic
potential
and
of
AS-IV
treating
ISO-induced
MF
mice,
employing
transcriptomics,
proteomics,
vitro,
vivo
experiments.
We
assessed
positive
effects
on
using
HE
staining,
Masson
ELISA,
immunohistochemical
transthoracic
echocardiography,
transmission
electron
microscopy,
DHE
fluorescence
staining.
Additionally,
we
elucidated
regulatory
role
through
comprehensive
transcriptomics
proteomics
analyses,
complemented
by
Western
blotting
RT-qPCR
validation
pertinent
pathways.
Our
findings
demonstrated
that
treatment
markedly
attenuated
myocardial
injury
oxidative
stress,
concomitantly
inhibiting
release
SASPs.
Furthermore,
integrated
analyses
revealed
mechanism
was
associated
with
regulating
cellular
senescence
p53
signaling
pathway.
These
results
highlight
exerts
not
only
stress
but
also
modulating
Dilated
cardiomyopathy
(DCM)
stands
as
one
of
the
most
prevalent
and
severe
causes
heart
failure.
Inflammation
plays
a
pivotal
role
throughout
progression
DCM
to
failure,
while
age
acts
natural
predisposing
factor
for
all
cardiovascular
diseases.
These
two
factors
often
interact,
contributing
cardiac
fibrosis,
which
is
both
common
manifestation
pathogenic
driver
adverse
remodeling
in
DCM-induced
Bulk
RNA-seq,
single-cell
Mendelian
randomization
analysis,
animal
model
construction,
BMP6
knockdown
were
utilized
identify
validate
potential
specific
markers
targets
intervention
We
found
that
hearts
exhibit
pronounced
inflammatory
cell
infiltration
fibrosis.
Both
bulk
RNA-seq
analyses
revealed
aberrant
expression
specifically
fibroblasts.
The
ROC
curve
underscores
high
specificity
relation
DCM,
analysis
further
confirms
protective
against
DCM.
Notably,
led
decrease
SMAD6
marked
elevation
COL1A1
levels,
indicating
its
antifibrotic
role.
emerges
promising
biomarker
functional
exerting
an
effect
therapeutic
target.
