bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 4, 2023
ABSTRACT
Tight
junctions
are
a
barrier-forming
cell-cell
adhesion
complex
and
have
been
proposed
to
regulate
cell
proliferation.
However,
the
underlying
mechanisms
not
well
understood.
Here,
we
used
cells
deficient
in
junction
scaffold
ZO-1
alone
or
together
with
its
paralog
ZO-2,
which
disrupts
junctional
barrier.
We
found
that
knockout
increased
proliferation,
loss
of
density-dependent
proliferation
control,
promoted
death.
These
phenotypes
were
enhanced
by
double
ZO-1/ZO-2
knockout.
Increased
was
dependent
on
YAP
ZONAB,
two
transcriptional
regulators.
stimulated
nuclear
translocation
activity
without
changes
Hippo-dependent
phosphorylation.
Knockout
TANK-binding
Kinase
1
(TBK1)
activation
expression
RhoA
activator
GEF-H1.
Knockdown
ZO-3,
another
interacting
ZO1,
sufficient
induce
GEF-H1
activity.
GEF-H1,
TBK1,
mechanotransduction
at
focal
adhesions
required
for
YAP/TEAD
ZO-1-deficient
cells.
Thus,
controls
Hippo-independent
activating
GEF-H1-
TBK1-regulated
mechanosensitive
signalling
network.
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 22, 2025
Background
Periplanta
americana
extract
(PAE),
a
traditional
Chinese
medicine
(TCM)
from
Shen
Nong
Ben
Cao
Jing
,
has
been
used
to
treat
ulcerative
colitis
(UC),
various
types
of
wounds
and
ulcers,
infantile
malnutrition,
palpitation,
asthma,
so
on.
However,
the
exact
mechanisms
PAE
in
UC
have
still
not
fully
revealed.
The
study
aims
explore
therapeutic
effects
UC.
Methods
efficacy
was
evaluated
using
DSS-induced
mice
model
colon
inflammation
mucosal
barrier
were
comprehensively
assessed.
Furthermore,
Network
pharmacological
analysis
utilized
identify
potential
targets
signaling
pathways
treatment.
proportion
markers
Th17
Treg
cells
spleen
examined.
signal
transduction
detected
vivo
.
In
vitro
an
activated
Notch1-mediated
Th17/Treg
modeled,
effect
on
epithelial
cell
Results
mitigated
intestinal
damage
mice.
showed
that
intervention
by
may
be
closely
related
differentiation,
IL-17
pathway,
cytokine-cytokine
receptor
interaction.
Mechanistically,
regulated
balance
inhibited
Notch1/Math1
pathway
alleviated
imbalance
Jurkat
T
cells.
After
notch1-activated
co-cultured
with
HCoEpic
cells,
expressions
Occludin,
ZO1
higher
Conclusion
could
alleviate
UC,
which
are
inhibition
Notch1
regulation
balance.
might
candidate
agent
for
Journal of Nanobiotechnology,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Jan. 29, 2025
Extracellular
membrane
vesicles
(EVs)
offer
promising
values
in
various
medical
fields,
e.g.,
as
biomarkers
liquid
biopsies
or
native
(or
bioengineered)
biological
nanocarriers
tissue
engineering,
regenerative
medicine
and
cancer
therapy.
Based
on
their
cellular
origin
EVs
can
vary
considerably
composition
diameter.
Cell
studies
mammalian
prominin-1,
a
cholesterol-binding
glycoprotein,
have
helped
to
reveal
new
donor
membranes
sources
of
EVs.
For
instance,
small
originate
from
microvilli
primary
cilia,
while
large
might
be
produced
by
transient
structures
such
retracting
extremities
cells
during
the
mitotic
rounding
process,
midbody
at
end
cytokinesis.
Here,
we
will
highlight
subcellular
origins
prominin-1+
EVs,
also
called
prominosomes,
potential
mechanism(s)
regulating
formation.
We
further
discuss
molecular
characteristics
notably
those
that
direct
effect
release
process
directly
implicated
cell
reprogramming
stem
cells.
Prominin-1+
mediate
intercellular
communication
embryonic
development
adult
homeostasis
healthy
individuals,
disseminating
information
diseases.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(5), P. 1808 - 1808
Published: Feb. 20, 2025
Repeated
exposure
to
low-level
blast
overpressure,
frequently
experienced
during
explosive
breaching
and
heavy
weapons
use
in
training
operations,
is
increasingly
recognised
as
a
serious
risk
the
neurological
health
of
military
personnel.
Although
research
on
underlying
pathobiological
mechanisms
humans
remains
limited,
this
study
investigated
effects
such
circulating
molecular
biomarkers
associated
with
inflammation,
neurovascular
damage,
endothelial
injury.
Blood
samples
from
breachers
were
analysed
for
myeloperoxidase
(MPO),
matrix
metalloproteinases
(MMPs),
junctional
proteins
indicative
blood-brain
barrier
(BBB)
disruption
including
occludin
(OCLN),
zonula
occludens-1
(ZO-1),
aquaporin-4
(AQP4),
syndecan-1
(SD-1).
The
results
revealed
significantly
elevated
levels
MPO,
MMP-3,
MMP-9,
MMP-10
compared
unexposed
controls,
suggesting
heightened
oxidative
stress,
vascular
Increased
OCLN
SD-1
further
indicated
BBB
glycocalyx
degradation
breachers.
These
findings
highlight
potential
chronic
unit
damage/dysfunction
repeated
underscore
importance
early
targeted
interventions-such
reducing
reinforcing
integrity,
managing
inflammation-that
could
be
essential
mitigating
long-term
impairment
exposure.
Cells,
Journal Year:
2024,
Volume and Issue:
13(7), P. 640 - 640
Published: April 5, 2024
Tight
junctions
are
a
barrier-forming
cell-cell
adhesion
complex
and
have
been
proposed
to
regulate
cell
proliferation.
However,
the
underlying
mechanisms
not
well
understood.
Here,
we
used
cells
deficient
in
junction
scaffold
ZO-1
alone
or
together
with
its
paralog
ZO-2,
which
disrupts
junctional
barrier.
We
found
that
knockout
increased
proliferation,
induced
loss
of
density-dependent
proliferation
control,
promoted
apoptosis
necrosis.
These
phenotypes
were
enhanced
by
double
ZO-1/ZO-2
knockout.
Increased
was
dependent
on
two
transcriptional
regulators:
YAP
ZONAB.
stimulated
nuclear
translocation
activity
without
changes
Hippo-dependent
phosphorylation.
Knockout
TANK-binding
kinase
1
(TBK1)
activation
expression
RhoA
activator
GEF-H1.
Knockdown
ZO-3,
another
interacting
ZO1,
sufficient
induce
GEF-H1
activity.
GEF-H1,
TBK1,
mechanotransduction
at
focal
adhesions
cooperate
activate
YAP/TEAD
ZO-1-deficient
cells.
Thus,
controled
Hippo-independent
activating
GEF-H1-
TBK1-regulated
mechanosensitive
signalling
network.
Toxicology in Vitro,
Journal Year:
2024,
Volume and Issue:
102, P. 105952 - 105952
Published: Oct. 11, 2024
Carcinogenic
N-nitroso
compounds,
especially
dimethylamine,
increase
the
risk
of
gastric
cancer
development.
Cytochrome
P450-2E1
metabolizes
this
compound,
thus
generating
an
oxidant
microenvironment.
We
aimed
to
evaluate
in
adenocarcinoma
cells
if
its
effect
on
CYP2E1
and
ROS
affects
signaling
pathways
associated
with
oncogenesis.
The
impact
N-
nitroso
dimethylamine
upon
activation/secretion
was
evaluated
by
DCFDA
assay
protocol,
TER
measurements,
Stat3,
pSTAT3,
ERK1/2,
pERK1/2
expression,
claudins-1
-6
finally
mRNA
values
IL-1β
IL-6,
IL-8
TNFα.
Our
results
showed
that
exposure
disrupts
regulation
Stat3
Erk1/2,
alters
expression
claudin-1
claudin-6
tight
junction
proteins,
increases
secretion
pro-inflammatory
cytokines.
These
alterations
induce
a
continuous
local
inflammatory
process,
event
identified
as
promoter.
In
summary,
can
disrupt
cell
mechanisms
Brain Research Bulletin,
Journal Year:
2023,
Volume and Issue:
206, P. 110836 - 110836
Published: Dec. 1, 2023
Protection
against
ischemic
stroke
may
be
most
effective
when
multiple
components
of
the
neurovascular
unit
are
protected,
yet
current
treatments
target
mainly
neurons.
Here
we
explored
whether
PSD-95
inhibitor
Tat-NR2B9c
(NA-1)
can
protect
not
only
neurons
but
also
blood-brain
barrier.
Adult
male
Sprague-Dawley
rats
were
randomly
divided
into
three
groups,
which
subjected
to
either
sham
surgery
or
transient
cerebral
ischemia-reperfusion,
after
some
animals
treated
with
Tat-NR2B9c.
The
therapeutic
efficacy
was
assessed
in
terms
degree
neurological
deficit
and
infarction,
integrity
barrier,
water
content,
as
well
expression
PSD-95,
nitric
oxide
synthase,
matrix
metalloprotease-9.
ameliorated
neurofunctional
deficit,
reduced
mitigated
barrier
injury
improved
its
following
leading
less
edema.
These
improvements
associated
upregulation
tight
junction
proteins
At
same
time,
downregulated
neuronal
synthase
metalloprotease-9,
while
reversing
ischemia-induced
downregulation
endothelial
brain.
We
report
here
first
evidence
that
is
expressed
vascular
cells
Our
experiments
a
rat
model
occlusion
middle
artery
suggest
mitigate
it
do
so
by
downregulating
metalloprotease-9
upregulating
synthase.
Frontiers in Cell and Developmental Biology,
Journal Year:
2024,
Volume and Issue:
12
Published: July 8, 2024
The
actin
cytoskeleton
regulates
the
integrity
and
repair
of
epithelial
barriers
by
mediating
assembly
tight
junctions
(TJs),
adherens
(AJs),
driving
wound
healing.
Actin
filaments
undergo
a
constant
turnover
guided
numerous
actin-binding
proteins,
however,
roles
filament
dynamics
in
regulating
intestinal
barrier
remain
poorly
understood.
Coactosin-like
protein
1
(COTL1)
is
member
ADF/cofilin
homology
domain
superfamily
that
binds
stabilizes
filaments.
COTL1
essential
for
neuronal
cancer
cell
migration,
its
functions
epithelia
unknown.
goal
this
study
to
investigate
structure,
permeability,
human
cells
(IEC).
was
found
be
enriched
at
apical
polarized
IEC
monolayers
vitro
.
knockdown
significantly
increased
paracellular
impaired
steady
state
TJ
AJ
integrity,
attenuated
junctional
reassembly
calcium-switch
model.
Consistently,
downregulation
expression
Drosophila
melanogaster
gut
permeability.
Loss
collective
migration
decreased
cell-matrix
attachment.
observed
abnormalities
COTL1-depleted
were
accompanied
cortical
actomyosin
cytoskeleton.
Overexpression
either
wild-type
or
deficient
mutant
tightened
activated
junction-associated
myosin
II.
Furthermore,
actin-uncoupled
inhibited
matrix
These
findings
highlight
as
novel
regulator
repair.
