Role of copper ion overload triggered by CD44 endocytosis on STAT3-mediated cuproptosis in septic myocardial injury
Abstract
Sepsis-induced
myocardial
injury
(SIMI)
is
a
severe
complication
in
sepsis
patients,
contributing
to
high
mortality
rates.
The
pathogenesis
remains
unclear,
but
emerging
evidence
suggests
copper
ion
overload
may
trigger
cell
death
via
"cuproptosis."
This
study
investigates
the
role
of
CD44,
glycoprotein
involved
inflammation
and
metal
uptake,
copper-induced
SIMI.
Using
an
LPS-induced
H9C2
cardiomyocyte
model,
we
found
CD44
expression
upregulated
SIMI,
correlating
with
increased
levels
oxidative
stress.
inhibition
reduced
mitigated
damage,
confirming
its
copper-mediated
injury.
Furthermore,
facilitated
uptake
into
mitochondria,
inducing
dysfunction
STAT3
pathway
activation.
overexpression
exacerbated
injury,
highlighting
critical
role.
These
findings
suggest
CD44-mediated
activation
contributes
positioning
as
potential
therapeutic
strategy
for
sepsis-induced
damage.
Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown
Published: May 7, 2025
Language: Английский