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.
Journal of Cell Science,
Journal Year:
2024,
Volume and Issue:
137(9)
Published: May 1, 2024
ABSTRACT
Tight
junctions
(TJs)
are
specialized
regions
of
contact
between
cells
epithelial
and
endothelial
tissues
that
form
selective
semipermeable
paracellular
barriers
establish
maintain
body
compartments
with
different
fluid
compositions.
As
such,
the
formation
TJs
represents
a
critical
step
in
metazoan
evolution,
allowing
multicompartmental
organisms
true,
barrier-forming
epithelia
endothelia.
In
six
decades
have
passed
since
first
observations
by
transmission
electron
microscopy,
much
progress
has
been
made
understanding
structure,
function,
molecular
composition
regulation
TJs.
The
goal
this
Perspective
is
to
highlight
key
concepts
emerged
through
research
future
challenges
lie
ahead
for
field.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 30, 2025
Abstract
Disruption
of
the
intestinal
epithelial
barrier
results
in
increased
permeability
and
is
a
key
factor
onset
progression
Crohn's
disease
(CD).
The
protein
SPARC
primarily
involved
cell
interaction
migration,
but
its
specific
role
remains
unclear.
This
study
demonstrates
that
significantly
overexpressed
both
CD
patients
murine
models
colitis.
Furthermore,
mice
deficient
exhibits
resistance
to
chemically
induced
colitis,
phenomenon
associated
with
modulation
barrier‐associated
proteins.
Mechanistically,
it
elucidated
competitively
binds
OTUD4
conjunction
MYD88,
facilitating
translocation
p65
from
cytoplasm
nucleus
subsequent
activation
p65‐MLCK/MLC2
pathway,
thereby
compromising
integrity.
Additionally,
identified
elevated
expression
regulated
via
METTL3‐YTHDF1
axis.
These
findings
indicate
levels
are
colitis‐induced
mice,
leading
damage
through
direct
MYD88/p65/MLCK/MLC2
signaling
pathway.
Consequently,
targeting
or
OTUD4/MYD88/p65/MLCK/MLC2
axis
may
offer
novel
insights
into
molecular
mechanisms
underlying
represent
potential
therapeutic
strategy.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2025,
Volume and Issue:
44(1)
Published: Feb. 7, 2025
Abstract
The
gut
microbiota
plays
a
crucial
role
in
safeguarding
host
health
and
driving
the
progression
of
intestinal
diseases.
Despite
recent
advances
remarkable
correlation
between
dysbiosis
extraintestinal
cancers,
underlying
mechanisms
are
yet
to
be
fully
elucidated.
Pathogenic
microbiota,
along
with
their
metabolites,
can
undermine
integrity
barrier
through
inflammatory
or
metabolic
pathways,
leading
increased
permeability
translocation
pathogens.
dissemination
pathogens
circulation
may
contribute
establishment
an
immune-suppressive
environment
that
promotes
carcinogenesis
organs
either
directly
indirectly.
oncogenic
cascade
always
engages
disruption
hormonal
regulation
responses,
induction
genomic
instability
mutations,
dysregulation
adult
stem
cell
proliferation.
This
review
aims
comprehensively
summarize
existing
evidence
points
potential
malignant
transformation
such
as
liver,
breast,
lung,
pancreas.
Additionally,
we
delve
into
limitations
inherent
current
methodologies,
particularly
challenges
associated
differentiating
low
loads
gut-derived
microbiome
within
tumors
from
sample
contamination
symbiotic
microorganisms.
Although
still
controversial,
understanding
contribution
translocated
metabolites
pathological
continuum
chronic
inflammation
could
offer
novel
foundation
for
development
targeted
therapeutics.
Biology,
Journal Year:
2025,
Volume and Issue:
14(3), P. 267 - 267
Published: March 6, 2025
Epithelial
linings
are
crucial
for
the
maintenance
of
physiological
barriers.
The
intestinal
epithelial
barrier
(IEB)
consists
enterocytes
through
tight
junctions
and
mucus-secreting
cells
can
undergo
modifications
throughout
life.
To
reproduce
as
closely
possible
IEB
main
features
over
time,
in
vitro
co-cultures
Caco2/HT-29
70/30
formed
by
parental
Caco2
HT-29
sub-cultivated
more
than
40
passages
were
set
up.
measurements
transepithelial
electrical
resistance
(TEER)
identified
two
populations:
TEER
(PC)
with
values
>
50
Ωcm2
fewer
passages,
leaky
(LC)
<
passages.
In
LC,
paracellular
permeability
increased
parallel.
By
immunofluorescence
Western
blot
analysis,
an
increase
claudin
2
was
observed
LC
vs.
PC,
no
differences
occludin
expression.
MUC-2
immunoreactivity
stronger
PC
LC.
also
showed
enhanced
vulnerability
to
TNFα+IFN-γ.
These
results
morpho-functional
reported
human
leaky/aged
gut
support
usefulness
our
cell
model
studying
molecular
processes
underlying
these
testing
drug/nutraceutical
treatments
ameliorate
aging.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Oct. 16, 2024
In
patients
with
rheumatoid
arthritis
(RA),
intestinal
flora
imbalance
and
butyrate
metabolism
disorders
precede
clinical
are
associated
the
pathogenesis
of
RA.
This
can
alter
immunology
permeability
mucosa,
leading
to
damage
barrier.
this
context,
bacteria
their
metabolites
enter
bloodstream
reach
distant
target
tissues
host,
resulting
in
local
inflammation
aggravating
arthritis.
Additionally,
is
also
exacerbated
by
bone
destruction
immune
tolerance
due
disturbed
differentiation
osteoclasts
adaptive
cells.
Of
note,
a
metabolite
flora,
which
not
only
locally
inhibits
immunity
targets
zonulin
tight
junction
proteins
alleviate
barrier-mediated
but
autoantibodies
balances
responses
T
B
lymphocytes
throughout
body
repress
erosion
inflammation.
Therefore,
key
intermediate
linking
host.
As
result,
restoring
butyrate-producing
capacity
using
exogenous
potential
therapeutic
strategies
for
RA
future.
Antioxidants,
Journal Year:
2025,
Volume and Issue:
14(3), P. 352 - 352
Published: March 18, 2025
(1)
Background:
Glucuronolactone
(GLU)
is
a
glucose
metabolite
with
antioxidant
activity.
At
present,
the
exact
role
of
it
in
regulating
intestinal
health
piglets
under
weaning
stress
not
clear.
The
purpose
this
study
to
investigate
effects
GLU
on
growth
performance
and
explore
potential
mechanisms.
(2)
Methods:
Twenty-four
weaned
were
randomly
assigned
into
two
groups,
one
group
receiving
basal
diet
other
an
experimental
supplemented
200
mg/kg
GLU.
(3)
Results:
increased
ADG,
ADFI,
final
body
weight
piglets,
while
reducing
diarrhea
rate.
Mechanistically,
alleviates
stress-induced
oxidative
inflammatory
responses
partly
through
activating
Nrf2-Akt
signaling
pathway
suppress
transcriptional
activity
FOXO1,
also
inhibiting
activation
TLR4-MAPK
reduce
secretion
pro-inflammatory
cytokines.
Moreover,
relative
abundance
Lactobacillus
reuteri
ileum
improved
composition
gut
microbiota.
(4)
Conclusions:
reduced
inflammation
Nrf2/Akt/FOXO1
health,
resulting
piglets.
