MGST1 Protects Pancreatic Ductal Cells from Inflammatory Damage in Acute Pancreatitis by Inhibiting Ferroptosis: Bioinformatics Analysis with Experimental Validation
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(5), P. 1899 - 1899
Published: Feb. 22, 2025
Numerous
animal
experiments
have
implicated
ferroptosis
in
the
pathogenesis
of
acute
pancreatitis
(AP).
Nonetheless,
due
to
sampling
constraints,
precise
role
human
body
during
AP
remains
elusive.
Method:
Peripheral
blood
sequencing
data
patients
with
(GSE194331)
were
obtained
from
Gene
Expression
Omnibus
(GEO)
database.
We
analyzed
differentially
expressed
genes
whose
expression
increased
or
decreased
increasing
disease
severity
and
intersected
them
gene
set
identify
ferroptosis-related
driver
for
disease.
The
hub
selected
using
machine
learning
algorithms,
a
nomogram
diagnosis
model
was
constructed.
Clinical
samples,
models,
an
vitro
experiment
also
used
validation.
investigation
unveiled
22
genes,
we
identified
three
AQP3,
TRIB2,
MGST1,
by
employing
two
algorithms.
AQP3
TRIB2
exhibit
robust
correlations
various
immune
cells.
constructed
utilizing
these
demonstrated
high
sensitivity
specificity
(AUC
=
0.889).
In
experiments,
discovered
first
time
that
occurs
pancreatic
duct
cells
pancreatitis,
MGST1
is
significantly
upregulated
cells,
where
it
plays
crucial
negatively
regulating
via
ACSL4/GPX4
axis.
addition,
overexpression
protects
ductal
inflammatory
damage.
our
investigation,
explored
mechanisms
AP.
These
results
highlight
potential
pathway
early
treatment
pancreatitis.
Language: Английский
CD36 Induces Inflammation by Promoting Ferroptosis in Pancreas, Epididymal Adipose Tissue, and Adipose Tissue Macrophages in Obesity-Related Severe Acute Pancreatitis
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(8), P. 3482 - 3482
Published: April 8, 2025
Severe
acute
pancreatitis
(SAP)
is
mainly
triggered
by
the
abnormal
activation
of
pancreatic
enzymes.
Obesity
acts
as
an
independent
risk
factor
for
SAP;
however,
underlying
mechanism
has
not
been
fully
elucidated.
In
this
study,
SAP
models
were
established
in
mice
with
normal
and
high-fat
diets.
Subsequently,
study
examined
ferroptosis
inflammatory
markers
pancreas
epididymal
adipose
tissues.
To
mimic
obesity-related
tissue
macrophages
(ATMs),
lipopolysaccharide
(LPS)
palmitic
acid
(PA)
introduced,
alterations
inflammation
assessed.
elucidate
regulatory
role
cluster
differentiation
36
(CD36)
ferroptosis,
liproxstatin-1
(Lip-1)
sulfosuccinimidyl
oleate
sodium
(SSO)
utilized
in-depth
analysis
pancreas,
tissues,
ATMs.
Our
findings
suggest
that
obesity
aggravates
tissue,
ATMs
during
SAP,
evidenced
increased
lipid
peroxidation,
elevated
Fe2+
levels,
markers,
while
these
regained
Lip-1.
Notably,
CD36
levels
significantly
ATMs,
indicating
promotes
induces
inflammation.
SSO
treatment
alleviated
changes
reduced
Western
blot
results
showed
promoted
through
acyl-CoA
synthetase
long-chain
family
member
4
(ACSL4)/glutathione
peroxidase
(GPX4)
axis
a
similar
was
mediated
ferritin
heavy
chain
1
(FTH1)/GPX4
These
demonstrate
facilitating
SAP.
The
inhibition
could
provide
novel
viewpoints
prevention
Language: Английский