Hepatocyte‐derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis
Wenqiang Xu,
No information about this author
Wenhui Mo,
No information about this author
Dengyu Han
No information about this author
et al.
Journal of Cellular and Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
28(8)
Published: March 23, 2024
Abstract
Liver
fibrosis
is
characterized
by
the
activation
and
transformation
of
hepatic
stellate
cells
(HSCs)
induced
various
injury
factors.
The
degree
liver
can
be
significantly
improved,
but
persistent
factors
present
a
significant
therapeutic
challenge.
Hepatocytes
are
most
important
parenchymal
cell
type
in
liver.
In
this
study,
we
explored
molecular
mechanisms
which
damaged
activate
HSCs
through
extracellular
vesicles.
We
established
coculture
model
LO2
LX2
validated
its
exosomal
transmission
activity.
Subsequently,
differentially
expressed
long
noncoding
RNAs
(lncRNAs)
were
screened
RNA
sequencing
their
action
as
competing
endogenous
(ceRNAs)
further
confirmed
using
biological
methods,
such
FISH
luciferase
assays.
Damaged
upregulation
fibrosis‐related
markers.
Exosomes
extracted
identified
from
supernatant
fraction
contained
lncRNA
cytoskeleton
regulator
(CYTOR)
that
competed
with
microRNA‐125
(miR‐125)
for
binding
to
glial
line‐derived
neurotrophic
factor
(GDNF)
HSCs,
turn,
promoting
activation.
MiR‐125
could
target
regulate
both
CYTOR
GDNF
vice
versa,
verified
assay.
an
vivo
model,
vesicles
formation
fibrosis.
Notably,
downregulation
within
effectively
inhibited
exosomes
upregulated
modulates
expression
downstream
activity
ceRNA,
providing
effective
mechanism
HSCs.
Language: Английский
Immune Checkpoints and the Immunology of Liver Fibrosis
Livers,
Journal Year:
2025,
Volume and Issue:
5(1), P. 5 - 5
Published: Jan. 27, 2025
Liver
fibrosis
is
a
very
complicated
dynamic
process
where
several
immune
cells
are
involved.
Both
innate
and
adaptive
immunity
implicated,
their
interplay
always
present.
Multi-directional
interactions
between
liver
macrophages,
hepatic
stellate
(HSCs),
cells,
cytokines
important
for
the
induction
perpetuation
of
fibrosis.
Detailed
studies
proteomics
transcriptomics
have
produced
new
evidence
role
individual
in
cirrhosis.
Most
these
controlled
by
various
checkpoints
whose
main
function
to
maintain
homeostasis
implicated
cells.
Recent
indicates
that
involved
In
particular,
programmed
cell
death
protein
1
(PD-1),
death-ligand
(PD-L1),
cytotoxic
T
lymphocyte-associated
antigen
4
(CTLA-4)
been
investigated,
particularly
after
availability
checkpoint
inhibitors.
Their
activation
leads
exhaustion
CD4+ve
CD8+ve
promotion
this
review,
current
pathogenesis
immunological
abnormalities
discussed.
The
recent
data
on
involvement
identified
as
possible
targets
future
interventions.
Language: Английский
Long non-coding RNAs: roles in cellular stress responses and epigenetic mechanisms regulating chromatin
Nucleus,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: May 22, 2024
Most
of
the
genome
is
transcribed
into
RNA
but
only
2%
sequence
codes
for
proteins.
Non-coding
transcripts
include
a
very
large
number
long
noncoding
RNAs
(lncRNAs).
A
growing
identified
lncRNAs
operate
in
cellular
stress
responses,
example
response
to
hypoxia,
genotoxic
stress,
and
oxidative
stress.
Additionally,
lncRNA
plays
important
roles
epigenetic
mechanisms
operating
at
chromatin
maintaining
architecture.
Here,
we
address
three
topics
that
have
had
significant
recent
advances.
The
first
an
emerging
role
many
responses.
second
development
high
throughput
screening
assays
develop
causal
relationships
between
across
with
functions.
Finally,
turn
advances
understanding
regulating
architecture
epigenetics,
build
on
some
earliest
work
linking
Language: Английский
Ghrelin alleviates liver fibrosis by triggering HSCs ferroptosis via regulating injured hepatocyte‐derived exosomal LncMALAT1/GPX4 pathway
Xin Luo,
No information about this author
Kan Chen,
No information about this author
Jie Zhang
No information about this author
et al.
The FASEB Journal,
Journal Year:
2025,
Volume and Issue:
39(2)
Published: Jan. 21, 2025
Abstract
Ghrelin
is
a
gastric
peptide
that
modulates
various
biological
functions,
including
potential
anti‐inflammatory
and
antifibrotic
properties.
Increasingly
evidence
have
demonstrated
exosomes
derived
from
injured
hepatocytes
(IHC‐Exo)
can
accelerate
the
activation
of
hepatic
stellate
cells
(HSCs)
liver
fibrosis.
Ferroptosis,
type
novel
programmed
cell
death,
regulates
diverse
pathological
processes,
However,
it
remains
unclear
whether
ghrelin
exerts
its
effect
through
mechanisms
involving
ferroptosis.
To
explore
mechanism,
IHC‐Exo
were
isolated
supernatant
mouse
primary
(HCs)
treated
with
palmitic
acid
(PA).
Mouse
HSCs
bile
duct
ligation
(BDL)‐induced
fibrosis
murine
model
then
or
ghrelin‐pretreated
(GHR‐IHC‐Exo).
The
expression
α‐SMA,
Collagen
I
long
noncoding
(lnc)
RNA
MALAT1
in
detected.
ferroptosis
was
evaluated
by
assessing
level
CCK8,
MDA,
GSH,
GPX4
expression.
serum
biopsy
samples
used
to
determine
involved
progression
Nanoparticle
tracking
analysis
electron
microscopy
characterized
features
IHC‐Exo.
As
results
suggested,
compared
IHC‐Exo,
GHR‐IHC‐Exo
treatment
significantly
promoted
HSCs,
inhibited
their
activation,
consequently
alleviated
BDL
mice.
inhibitory
on
partially
reversed
inhibitor
Ferrostatin‐1.
lncMALAT1
down‐regulated
as
Serum
exosome
levels
higher
patients
severe
those
mild
Additionally,
suppressor
protein
elevated
progression,
indicating
decreased
In
conclusion,
reduced
pro‐fibrotic
regulating
lncMALAT1/GPX4
pathway
mediated
Triggering
via
may
become
strategy
alleviate
Language: Английский
Exosomes: A Promising Drug Delivery Tool in Hepatic Drug Delivery
Journal of Drug Delivery Science and Technology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 106761 - 106761
Published: March 1, 2025
Language: Английский
Dynamic role of exosomal long non-coding RNA in liver diseases: pathogenesis and diagnostic aspects
Mohammed Ismail,
No information about this author
M Fadul,
No information about this author
Reham Taha
No information about this author
et al.
Hepatology International,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 21, 2024
Language: Английский
The role of hepatocyte-derived extracellular vesicles in liver and extrahepatic diseases
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
180, P. 117502 - 117502
Published: Oct. 1, 2024
Language: Английский
Exosome-mediated Transfer of lncRNA in Liver Associated Diseases; Uncovered Truths
Raed Obaid Saleh,
No information about this author
Hamad Ali Hamad,
No information about this author
Maryam Abdulrahman Najim
No information about this author
et al.
Cell Biochemistry and Biophysics,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 20, 2024
Language: Английский
Extracellular Vesicles in Viral Liver Diseases
Viruses,
Journal Year:
2024,
Volume and Issue:
16(11), P. 1785 - 1785
Published: Nov. 17, 2024
Extracellular
vesicles
(EVs)
are
bilayer
released
by
cells
in
the
microenvironment
of
liver
including
parenchymal
and
non-parenchymal
cells.
They
third
important
mechanism
communications
between
cells,
besides
secretion
cytokines
chemokines
direct
cell-to-cell
contact.
The
aim
this
review
is
to
discuss
role
EVs
viral
disease,
as
there
increasing
evidence
that
transportation
proteins,
all
types
RNA,
particles
complete
virions
implicated
pathogenesis
both
cirrhosis
viral-related
hepatocellular
carcinoma.
biogenesis
discussed
their
diseases
presented.
Their
use
diagnostic
prognostic
biomarkers
also
analyzed.
Most
importantly,
significance
possible
novel
treatment
strategies
for
fibrosis
carcinoma
presented,
although
available
data
based
on
experimental
clinical
trials
have
not
been
reported.
Language: Английский