Journal of Cellular and Molecular Medicine,
Год журнала:
2025,
Номер
29(5)
Опубликована: Март 1, 2025
ABSTRACT
Recent
research
has
revealed
a
close
association
between
obesity
and
various
metabolic
disorders,
including
renal
diseases,
but
the
mechanism
is
still
unknown.
This
study
explored
role
of
p16INK4a
in
obesity‐related
kidney
fibrosis
evaluated
its
potential
as
therapeutic
target.
Using
wild‐type
(WT)
mice
p16
KO
mice,
we
fed
both
groups
high‐fat
diet
(HFD)
for
6
months.
Our
results
showed
that
an
HFD
led
to
significant
weight
gain
increased
expression
WT
mouse
kidneys.
Notably,
presented
reduced
fibrosis,
indicated
by
decreased
levels
profibrotic
proteins
(α‐SMA
collagen
I)
improved
histological
outcomes,
glomeruli
tubules.
P16
also
suppressed
several
proinflammatory
biomarkers
(MMP1,
MMP3,
IL‐1β,
TNF‐α
IL‐6)
inhibited
NLRP3
inflammasome
pathway.
The
administration
ABT263
further
validated
these
findings
decreasing
inflammation
HFD‐fed
suggesting
contributes
fibrotic
inflammatory
processes.
Metabolomic
analyses
knockout
influenced
pathways,
linoleic
acid
pyrimidine
metabolism,
HFD‐induced
Additionally,
over‐expression
was
observed
kidneys
chronic
disease
patients
with
long‐term
hyperlipidaemia.
These
highlight
critical
obesity‐induced
damage
suggest
targeting
may
be
promising
approach
treating
inflammation.
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(3), С. 968 - 986
Опубликована: Янв. 1, 2024
Idiopathic
pulmonary
fibrosis
(IPF)
is
characterized
by
fibrotic
matrix
deposition
and
irreversible
aberrant
tissue
remodeling.Their
mechanisms
of
action
are
associated
with
the
activation
macrophages
a
disturbed
immune
environment.We
aim
to
determine
how
these
activated
influenced
pathogenesis
fibrosis.We
found
areas
IPF
patients
contained
more
serum
glucocorticoid-induced
kinase
1
(SGK1)-positive
M2-type
macrophages.Similarly,
bleomycin
(BLM)+LPS
significantly
triggered
high
expression
SGK1
in
mice,
accompanied
destroyed
lung
structure
function,
increased
markers
microenvironment.Mechanistically,
markedly
promoted
reprogramming
lungs
triggering
glycogen
synthase
3beta
(GSK3β)-tat-interacting
protein
60
(TIP60)-histone-3
lysine-27
acetylation
(H3K27ac)
signalings,
which
further
released
chemokine
(C-C
motif)
ligand
9
(CCL9)
attract
Th17
cells
delivered
TGF-β
fibroblasts
for
synergistically
destroying
microenvironment,
was
largely
reversed
macrophage
depletion
mice.We
took
as
entry
point
deeply
analyze
provided
insights
development
novel
drugs
represented
SGK1.
Heliyon,
Год журнала:
2023,
Номер
9(11), С. e22154 - e22154
Опубликована: Ноя. 1, 2023
The
incidence
of
acute
myocardial
infarction
(AMI)
is
increasing
yearly.
With
the
use
thrombolysis
or
percutaneous
coronary
intervention
(PCI),
mortality
rate
has
been
significantly
reduced.
However,
reperfusion
can
cause
additional
injury.
There
still
a
lack
effective
drugs
to
treat
I/R
injury,
and
it
urgent
find
new
therapeutic
drugs.In
this
study,
network
pharmacology
was
used
predict
potential
targets
biological
processes
involved
in
Muscone-mediated
treatment
infarction.
To
model
ischemia‒reperfusion
hypoxia-reoxygenation
vivo
injury
C57BL/6
mice
constructed.
Mice
were
treated
with
Muscone
i.p.
for
4
weeks.
We
detected
cardiac
function
on
day
28.The
expression
levels
apoptotic
proteins
Caspase-3
Bax
anti-apoptotic
protein
Bcl-2
by
immunoblotting
after
AC16
cells
vivo.
Additionally,
gene
PUMA
p53
analyzed
qRT‒PCR.
Molecular
docking
evaluate
binding
energy
between
NLRP3-related
proteins.
Immunoblotting
qRT‒PCR
assess
NLRP3
signaling
pathway-related
(NLRP3,
ASC,
Caspase-1)
gene,
respectively.
Moreover,
extracellular
acidification
measured
using
Seahorse
system
glycolysis
treatment.
key
glycolytic
enzyme
PKM2
Finally,
ChIP‒qPCR
performed
determine
histone
modifications
(H3K4me3,
H3K27me3,
H2AK119Ub)
promoter
region.GO
functional
enrichment
analysis
revealed
that
muscone
regulating
(BP)
AMI,
which
mainly
included
negative
regulation
apoptosis
pathway,
response
lipopolysaccharide,
blood
pressure
regulation.
cellular
components
(CC)
muscone-mediated
AMI
lipid
rafts,
membrane
microdomains,
regions.
molecular
functions
(MF)
oxidoreductase
activity,
nuclear
receptor
transcription
factor
activity.
In
vitro
results
indicated
could
inhibit
while
level
antiapoptotic
Bcl-2.
suppressed
cells.
suggested
bind
well
Cryo-EM
structure
NEK7(PDB
ID:6NPY).
Further
investigation
inflammatory
pathways
reduce
Caspase-1
Caspase
recruitment
domain.
Fluorescent
quantitative
PCR
experiments
showed
inhibited
NLRP3.
we
found
enhance
efficiency
cells,
may
be
related
increased
increase
PKM2.
Chromatin
immunoprecipitation
assays
H3K4me3
region
H3K27me3
H2AK119Ub
region.Muscone
promoted
pathway
activation
improve
