EBioMedicine,
Journal Year:
2024,
Volume and Issue:
102, P. 105088 - 105088
Published: March 26, 2024
Metabolic
dysfunction-associated
steatohepatitis
(MASH)
is
characterised
by
cell
death
of
parenchymal
liver
cells
which
interact
with
their
microenvironment
to
drive
disease
activity
and
fibrosis.
The
identification
the
major
type
could
pave
way
towards
pharmacotherapy
for
MASH.
To
date,
increasing
evidence
suggest
a
regulated
death,
named
ferroptosis,
occurs
through
iron-catalysed
peroxidation
polyunsaturated
fatty
acids
(PUFA)
in
membrane
phospholipids.
Lipid
enjoys
renewed
interest
light
as
druggable
target
This
review
recapitulates
molecular
mechanisms
ferroptosis
physiology,
human
MASH
critically
appraises
results
targeting
preclinical
models.
Rewiring
redox,
iron
PUFA
metabolism
creates
proferroptotic
environment
involved
MASH-related
hepatocellular
carcinoma
(HCC)
development.
Ferroptosis
induction
might
be
promising
novel
approach
eradicate
HCC,
while
its
inhibition
ameliorate
progression.
Cell,
Journal Year:
2022,
Volume and Issue:
185(2), P. 379 - 396.e38
Published: Jan. 1, 2022
The
liver
is
the
largest
solid
organ
in
body,
yet
it
remains
incompletely
characterized.
Here
we
present
a
spatial
proteogenomic
atlas
of
healthy
and
obese
human
murine
combining
single-cell
CITE-seq,
single-nuclei
sequencing,
transcriptomics,
proteomics.
By
integrating
these
multi-omic
datasets,
provide
validated
strategies
to
reliably
discriminate
localize
all
hepatic
cells,
including
population
lipid-associated
macrophages
(LAMs)
at
bile
ducts.
We
then
align
this
across
seven
species,
revealing
conserved
program
bona
fide
Kupffer
cells
LAMs.
also
uncover
respective
spatially
resolved
cellular
niches
microenvironmental
circuits
driving
their
unique
transcriptomic
identities.
demonstrate
that
LAMs
are
induced
by
local
lipid
exposure,
leading
induction
steatotic
regions
liver,
while
cell
development
crucially
depends
on
cross-talk
with
stellate
via
evolutionarily
ALK1-BMP9/10
axis.
Science Immunology,
Journal Year:
2023,
Volume and Issue:
8(82)
Published: April 7, 2023
Macrophages
are
central
orchestrators
of
the
tissue
response
to
injury,
with
distinct
macrophage
activation
states
playing
key
roles
in
fibrosis
progression
and
resolution.
Identifying
populations
found
human
fibrotic
tissues
could
lead
new
treatments
for
fibrosis.
Here,
we
used
liver
lung
single-cell
RNA
sequencing
datasets
identify
a
subset
CD9+TREM2+
macrophages
that
express
SPP1,
GPNMB,
FABP5,
CD63.
In
both
murine
hepatic
pulmonary
fibrosis,
these
were
enriched
at
outside
edges
scarring
adjacent
activated
mesenchymal
cells.
Neutrophils
expressing
MMP9,
which
participates
TGF-β1,
type
3
cytokines
GM-CSF
IL-17A
coclustered
macrophages.
vitro,
GM-CSF,
IL-17A,
TGF-β1
drive
differentiation
monocytes
into
scar-associated
markers.
Such
differentiated
cells
degrade
collagen
IV
but
not
I
promote
TGF-β1-induced
deposition
by
models
blocking
or
reduced
expansion
Our
work
identifies
highly
specific
population
assign
profibrotic
role
across
species
tissues.
It
further
provides
strategy
unbiased
discovery,
triage,
preclinical
validation
therapeutic
targets
based
on
this
fibrogenic
population.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(9), P. 1653 - 1653
Published: Aug. 22, 2023
The
liver
is
an
organ
that
particularly
exposed
to
reactive
oxygen
species
(ROS),
which
not
only
arise
during
metabolic
functions
but
also
the
biotransformation
of
xenobiotics.
disruption
redox
balance
causes
oxidative
stress,
affects
function,
modulates
inflammatory
pathways
and
contributes
disease.
Thus,
stress
implicated
in
acute
injury
pathogenesis
prevalent
infectious
or
chronic
diseases
such
as
viral
hepatitis
B
C,
alcoholic
fatty
disease,
non-alcoholic
disease
(NAFLD)
steatohepatitis
(NASH).
Moreover,
plays
a
crucial
role
progression
fibrosis,
cirrhosis
hepatocellular
carcinoma
(HCC).
Herein,
we
provide
overview
on
effects
pathophysiology
mechanisms
by
promotes
