Versican binds collagen via its G3 domain and regulates the organization and mechanics of collagenous matrices
Journal of Biological Chemistry,
Год журнала:
2024,
Номер
300(12), С. 107968 - 107968
Опубликована: Ноя. 5, 2024
Язык: Английский
Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling
Proteoglycan Research,
Год журнала:
2024,
Номер
2(4)
Опубликована: Окт. 1, 2024
Proteoglycans
and
their
proteolytic
fragments
diffuse
into
biological
fluids
such
as
plasma,
serum,
urine,
or
synovial
fluid,
where
they
can
be
detected
by
antibodies
mass-spectrometry.
Neopeptides
generated
the
proteolysis
of
proteoglycans
are
recognized
specific
neoepitope
act
a
proxy
for
activity
certain
proteases.
Proteoglycan
proteoglycan
potentially
used
prognostic,
diagnostic,
theragnostic
biomarkers
several
diseases
characterized
dysregulated
extracellular
matrix
remodeling
osteoarthritis,
rheumatoid
arthritis,
atherosclerosis,
thoracic
aortic
aneurysms,
central
nervous
system
disorders,
viral
infections,
cancer.
Here,
we
review
main
mechanisms
accounting
presence
soluble
in
fluids,
potential
application
biomarkers,
highlight
challenges
opportunities
ahead
clinical
translation.
Язык: Английский
Mediating Mendelian randomization in the proteome identified potential drug targets for obesity-related allergic asthma
Hereditas,
Год журнала:
2025,
Номер
162(1)
Опубликована: Фев. 1, 2025
With
the
development
of
economy,
number
obese
patients
has
been
increasing
annually
worldwide.
The
proportion
asthma
associated
with
obesity
is
also
gradually
rising.
However,
pathogenesis
obesity-related
remains
incompletely
understood,
and
conventional
pharmacological
treatments
generally
show
limited
efficacy.
This
study
aims
to
explore
causal
relationship
between
allergic
asthma,
elucidate
identify
plasma
proteins
involved
in
its
development,
providing
new
insights
for
clinical
interventions.
In
this
study,
we
employed
a
two-step
approach
mediation
Mendelian
randomization
(MR)
analysis,
utilizing
stringent
selection
criteria
instrumental
variables
(IVs).
was
used
assess
impact
on
validate
identified
as
mediating
factors.
We
further
explored
functions
enriched
pathways
using
Gene
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
analyses.
Finally,
conducted
drug-targeted
MR
analysis
evaluate
potential
each
mediator
drug
target
gene.
If
significant
heterogeneity
remained
among
IVs,
applied
weighted
median
method
primary
analytical
tool.
Otherwise,
utilized
inverse
variance
(IVW)
main
approach.
Additionally,
various
sensitivity
analyses
statistical
tests
illustrate
robustness
observed
associations.
research
findings
indicate
asthma.
Plasma
such
TPST1,
ROR1,
DAPK1
mediate
relationship,
TPST1
accounting
over
10%
effect.
GO
KEGG
that
genes
corresponding
these
are
primarily
related
responses
stimuli,
carbohydrate
synthesis
metabolism,
regulation
certain
protein
activities,
synaptic
connections.
suggests
SIGLEC12,
BOLA1,
HOMER2,
all
have
be
genes.
defined
by
BMI
may
promote
influencing
expression
DAPK1.
Furthermore,
some
proteins,
including
could
potentially
serve
therapeutic
targets
treating
patients.
needed
their
mechanisms
underlying
effects.
Not
applicable.
Язык: Английский
Stromal Versican Accumulation and Proteolysis Regulate the Infiltration of CD8+ T Cells in Breast Cancer
Cancers,
Год журнала:
2025,
Номер
17(9), С. 1435 - 1435
Опубликована: Апрель 25, 2025
Background/Objectives:
Recent
clinical
trials
in
breast
cancer
have
demonstrated
that
some
patients
benefit
from
immune
checkpoint
blockade,
though
better
predictive
markers
are
needed.
The
accumulation
of
the
immunomodulatory
matrix
proteoglycan
versican
(VCAN)
can
predict
exclusion
CD8+
tumor-infiltrating
lymphocytes
(TILs)
settings
and,
thus,
is
evaluated
here.
Methods:
A
total
230
cancers
were
analyzed
for
VCAN
accumulation,
proteolysis,
and
TILs.
TILs
categorized
based
on
their
localization
tumor
epithelial
or
stromal
compartments.
Results:
was
detected
90%
cancers,
more
commonly
ER+
tumors
(93%
vs.
77%;
p
<
0.001).
MCF7
cells
treated
with
estrogen
upregulate
without
an
enhanced
expression
ADAMTS-proteases.
VCAN-undetectable
demonstrate
greater
compared
to
VCAN-detectable
(p
=
0.012).
T
within
TNBC
high
proteolysis
infiltrated
compartment
often
than
low
(91%
42%
respectively;
0.008).
In
TCGA
cohort,
a
strong
inverse
correlation
between
CD8A
observed
across
subtypes.
Conclusions:
correlates
subtypes
cancer,
warranting
further
validation
as
biomarkers
immunotherapy.
Язык: Английский
Drivers of Spatial Immune Heterogeneity in a Mouse Tumor Model after Immunotherapy
Опубликована: Янв. 1, 2024
Язык: Английский
Spatial immune heterogeneity in a mouse tumor model after immunotherapy
Cancer Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 3, 2024
Abstract
Cancer
immunotherapy
is
increasingly
used
in
clinical
practice,
but
its
success
rate
reduced
by
tumor
escape
from
the
immune
system.
This
may
be
due
to
genetic
instability
of
cells,
which
allows
them
adapt
response
and
leads
intratumoral
heterogeneity.
The
study
investigated
spatial
heterogeneity
microenvironment
possible
drivers
a
mouse
model
tumors
induced
human
papillomaviruses
(HPV)
following
immunotherapy.
Gene
expression
was
determined
RNA
sequencing
mutations
whole
exome
sequencing.
A
comparison
different
areas
revealed
cell
infiltration,
gene
expression,
mutation
composition.
While
mean
numbers
with
every
impact
on
or
protein
function
were
comparable
treated
control
tumors,
high
moderate
increased
after
genes
mutated
significantly
enriched
associated
ECM
metabolism,
degradation,
interactions,
HPV
infection
carcinogenesis,
processes
such
as
antigen
processing
presentation,
Toll‐like
receptor
signaling,
cytokine
production.
analysis
DNA
damage
repair
factors
that
upregulated
Apobec1
Apobec3
downregulated
related
homologous
recombination
translesion
synthesis.
In
conclusion,
this
describes
heterogeneity,
could
lead
escape,
suggests
potential
mechanisms
involved.
Язык: Английский
Tumour’s Digest: Macrophage metabolism creates a barrier to T cells
Cancer Research,
Год журнала:
2024,
Номер
84(20), С. 3322 - 3323
Опубликована: Авг. 26, 2024
Changes
in
the
composition
and
physical
properties
of
tumor
extracellular
matrix
are
linked
to
poor
cytotoxic
T-cell
infiltration
therapy
response,
yet
underlying
mechanisms
remain
unclear.
Tharp
colleagues
revealed
a
fascinating
cascade
where
fibrosis
alters
macrophage
metabolism,
restricting
nutrients
available
infiltrating
T
cells
resulting
their
suppression
exclusion
from
microenvironment.
This
study
suggests
that
targeting
metabolic
pathways
could
be
promising
strategy
overcome
immune
induced
by
matrix.
Язык: Английский