Role of TMEM230 in the Aberrant Glycosylation in Human Autoimmunity and Cancer
Proteoglycan Research,
Год журнала:
2025,
Номер
3(1)
Опубликована: Янв. 1, 2025
ABSTRACT
Alterations
in
glycoconjugate
profiles
are
thought
to
promote
changes
cell‐to‐cell
and
cell‐to‐intracellular
extracellular
scaffold
interactions
human
disease.
The
nearly
unlimited
number
of
“glycoforms”
that
may
exist
nature
difficult
study
due
glycosylation
modifications
being
associated
with
non‐genome
coded
posttranscription
post‐translation
processes.
Specific
products
generated
by
dependent
on
concentration
sub‐cellular
locations
glycan
synthesis
processing
enzymes.
An
indirect
“high‐throughput”
approach
is
characterize
enzymes
(hydrolases
transferases)
single
cell
sequencing
all
types
tissue
diseases.
We
previously
identified
TMEM230
as
an
endoplasmic
reticulum
(ER)
protein
regulates
NOTCH
glycoprotein
receptor
ligand
signaling
zebrafish
blood
vessel
formation
destructive
remodeling
capacities
diverse
including
fibroblast,
phagocytic
immune
system
cells
patients
cancer
or
granulomatous
systemic
vasculitis
autoimmune
disorder.
represents
a
paradigm
mediated
signal
transduction
supports
the
role
modifications.
ER
initiates
earliest
steps
synthesis,
sorting,
trafficking.
As
remodeling,
Notch
hallmarks
disorders,
we
investigated
whether
aberrant
expression
was
also
rheumatoid
arthritis
(RA).
In
this
current
study,
analysis
supported
downregulated
synovial
RA
while
were
predominantly
upregulated.
contrast,
upregulated
high‐grade
compared
low‐grade
gliomas
it
N‐linked
(GlcNAc),
glycosaminoglycan
expression.
Our
collective
results
support
glycan/glycoconjugate
aggressive
gliomas.
therefore
be
therapeutic
target
marker
for
clinical
treatment
induced
autoimmunity
disorders
cancer.
Язык: Английский
Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(21), С. 11382 - 11382
Опубликована: Окт. 23, 2024
Calciprotein
particles
(CPPs)
are
essential
circulating
scavengers
of
excessive
Ca
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
Comprehensive Investigation of Proteoglycan Gene Expression in Breast Cancer: Discovery of a Unique Proteoglycan Gene Signature Linked to the Malignant Phenotype
Proteoglycan Research,
Год журнала:
2025,
Номер
3(1)
Опубликована: Янв. 1, 2025
Solid
tumors
present
a
formidable
challenge
in
oncology,
necessitating
innovative
approaches
to
improve
therapeutic
outcomes.
Proteoglycans,
multifaceted
molecules
within
the
tumor
microenvironment,
have
garnered
attention
due
their
diverse
roles
cancer
progression.
Their
unique
ability
interact
with
specific
membrane
receptors,
growth
factors,
and
cytokines
provides
promising
avenue
for
development
of
recombinant
proteoglycan-based
therapies
that
could
enhance
precision
efficacy
treatment.
In
this
study,
we
performed
comprehensive
analysis
proteoglycan
gene
landscape
human
breast
carcinomas.
Leveraging
available
wealth
genomic
clinical
data
regarding
expression
carcinoma
using
machine
learning
model,
identified
signature
composed
five
proteoglycans
differentially
modulated
tissue:
Syndecan-1
asporin
(upregulated)
decorin,
PRELP
podocan
(downregulated).
Additional
query
revealed
serglycin,
previously
shown
be
increased
patients
mouse
models
correlate
poor
prognosis,
was
indeed
decreased
vast
majority
its
levels
inversely
correlated
progression
invasion.
This
provide
novel
diagnostic
capabilities
biology
highlights
need
further
utilization
publicly
datasets
validation
preclinical
experimental
results.
Язык: Английский
Decoding glycosylation in cardiovascular diseases: mechanisms, biomarkers, and therapeutic opportunities
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Май 19, 2025
Protein
glycosylation,
particularly
O-GlcNAcylation,
is
a
critical
post-translational
modification
(PTM)
that
regulates
cardiac
and
vascular
functions
by
modulating
protein
stability,
localization,
interactions.
Dysregulated
glycosylation
generally
believed
as
key
driver
in
the
pathogenesis
of
cardiovascular
diseases
(CVDs),
contributing
to
adverse
remodeling,
mitochondrial
dysfunction,
metabolic
dysregulation,
inflammation.
This
review
highlights
mechanistic
roles
CVD
progression,
including
its
regulation
study
explored
dual
role
O-GlcNAcylation
acute
protection
chronic
injury,
emphasizing
potential
biomarker
for
early
diagnosis
risk
stratification.
Therapeutic
strategies
targeting
pathways,
O-GlcNAc
transferase
(OGT),
O-GlcNAcase
(OGA),
hold
promise
addressing
myocardial
ischemia-reperfusion
diabetic
cardiomyopathy,
atherosclerosis.
Advances
profiling
interdisciplinary
collaboration
are
essential
overcome
challenges
such
tissue
specificity
off-target
effects,
advancing
precision
medicine.
Язык: Английский
Towards a Better Understanding of the Influence of Carbohydrates on the Structural, Dynamic, and Functional Properties of Fibromodulin: Crucial Insights From a Comparative In Silico Approach
Proteoglycan Research,
Год журнала:
2024,
Номер
2(4)
Опубликована: Окт. 1, 2024
ABSTRACT
Proteoglycans
are
a
class
of
biological
macromolecules
that
characterized
by
the
presence
long
chains
negatively
charged
glycosaminoglycans
(GAGs).
One
family
proteoglycans,
small
leucine‐rich
proteoglycans
(SLRPs),
is
well‐conserved
proteins,
which
predominantly
present
in
extracellular
matrix
and
critical
components
numerous
processes
matrix.
Interestingly,
fibromodulin
(FMOD),
one
members
SLRP
exists
both
as
proteoglycan
glycoprotein
juveniles
old‐aged
individuals,
respectively.
Despite
their
physiological
significance
interesting
variations
carbohydrate
composition,
structural
dynamics
(e.g.,
evolution
structure
over
time),
3D
conformational
preferences
remains
unexplored
to
date.
In
this
study,
molecular
modeling
techniques
were
used
investigate
effects
changes
composition
on
dynamics.
A
total
6µs
all‐atom
simulations
performed
three
types
systems:
non‐glycosylated
FMOD,
form
lacking
keratan
sulfate
disaccharides
with
GAGs.
Substantial
found
FMOD
between
states.
These
accompanied
modifications
curved‐solenoid
architecture
well
local
solvent
accessibilities
some
residues.
relatively
rigid,
motif,
sequence
across
various
species,
was
identified
unstructured
N‐terminal
domain.
This
motif
highly
accessible
states,
despite
its
proximity
chains.
two
features
(rigididy
high
accessibility)
suggest
key
role
for
protein‐protein
interactions
established
Fibromodulin.
Overall,
study
provides
insight
into
how
influences
protein
functions.
Язык: Английский