Increased melanin induces aberrant keratinocyte − melanocyte − basal − fibroblast cell communication and fibrogenesis by inducing iron overload and ferroptosis resistance in keloids
Cell Communication and Signaling,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 18, 2025
Keloid
is
a
typical
skin
fibrotic
disease
with
unclear
mechanisms
and
limited
therapeutic
options.
Fibroblast-induced
fibrogenesis
crucial
cause
of
KD.
However,
the
types
cells
involved
in
fibroblast
KD
specific
are
unclear.
This
study
aimed
to
investigate
role
melanocyte-secreted
melanin
promoting
its
mechanism
evaluate
potential
effect
intervening
treating
keloid.
The
activity
pigmentation-related
pathways
melanocytes
was
examined
using
single-cell
RNA-sequence
(scRNA-seq)
analysis.
Masson-Fontana
staining
or
isolated
quantification
detected
levels
distribution
cells.
Collagen
deposition,
wounding
healing,
proliferation
analysis
were
employed
integratively
assess
fibrogenesis.
After
treatment,
bulk-seq
identified
fibroblasts'
differentially
expressed
genes
(DEGs).
iron
by
Perl's
quantification.
Cell
viability,
LipidROS,
malondialdehyde
assay
accessed
ferroptosis
levels.
ML329
evaluated
keloid-bearing
mice.
We
found
enriched
keloid
further
validated
increased
patients.
Additionally,
positively
correlated
Area
Severity
Index
Furthermore,
significantly
promoted
proliferation,
migration,
collagen
synthesis.
Mechanically,
basal
cell
permeability
inflammation
facilitate
transfer
dermis,
where
it
activated
fibroblasts
evoking
overload
resistance.
Consistently,
resistance
primary
tissues
Inhibition
effectively
diminish
melanin-induced
Interestingly,
induced
an
autocrine
manner
stimulated
keratinocytes
take
up
deepen
color
upregulating
F2R-like
trypsin
receptor
1
(F2RL1).
In
vivo,
delivery
ML329,
microphthalmia-associated
transcription
factor
(MITF)
inhibitor,
could
suppress
melanogenesis
alleviate
human
nude
Meanwhile,
decreased
content
restored
sensitivities
ferroptosis.
Collectively,
melanin-lowing
strategies
may
appear
as
new
target
for
Current
treatments
ineffective.
Our
research
demonstrates
that
increase
patients
play
significant
progression
mediating
aberrant
keratinocyte
−
melanocyte
crosstalk.
Importantly,
we
pharmacological
inhibition
MITF
shows
promise
alleviating
keloid,
offering
breakthrough
treatment.
synthesis
pathway
abnormally
melanocytes.
Melanin
destroys
membrane
barrier
triggering
translocates
dermal
layers
paracrine
induce
overgrowth,
ECM
deposition
inducing
maintains
melanocytes'
hyperproliferative
non-immortal
properties
manner.
It
enhances
keratocyte
PAR-2
promote
transit
superficial
epidermis
layers,
which
be
related
deepening
color.
alleviates
Язык: Английский
The emerging role and therapeutical implications of ferroptosis in wound healing
Burns & Trauma,
Год журнала:
2025,
Номер
13
Опубликована: Янв. 1, 2025
Abstract
Wound
healing
is
a
complex
biological
process
involving
multiple
steps,
including
hemostasis,
inflammation,
proliferation,
and
remodeling.
A
novel
form
of
regulated
cell
death,
ferroptosis,
has
garnered
attention
because
its
involvement
in
these
processes.
Ferroptosis
characterized
by
the
accumulation
lipid
peroxides
tightly
metabolism,
iron
lipid-peroxide
repair
network,
all
which
exert
significant
influence
on
wound
healing.
This
review
highlights
current
findings
emerging
concepts
regarding
multifaceted
roles
ferroptosis
throughout
stages
normal
chronic
Additionally,
potential
targeted
interventions
aimed
at
modulating
to
improve
wound-healing
outcomes
discussed.
Язык: Английский
Promoting scarless wound closure utilizing an injectable thermosensitive hydrogel with anti-inflammatory, antioxidant, and scar formation inhibiting properties
Biomaterials Advances,
Год журнала:
2025,
Номер
unknown, С. 214295 - 214295
Опубликована: Март 1, 2025
Язык: Английский
The Role of JPX in Regulating FUS/SLC7A11 Signaling Pathway Mediated Ferroptosis in Keloid Fibroblasts and its Potential in Scar Repair
Biochemical and Biophysical Research Communications,
Год журнала:
2025,
Номер
unknown, С. 151770 - 151770
Опубликована: Апрель 1, 2025
Язык: Английский
Ferroptosis in idiopathic pulmonary fibrosis: mechanisms, impact, and therapeutic opportunities
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 21, 2025
Idiopathic
pulmonary
fibrosis
(IPF)
is
a
fatal
interstitial
lung
disease
characterized
by
progressive
scarring,
alveolar
destruction,
and
limited
therapeutic
options.
Although
the
exact
etiology
of
IPF
remains
unclear,
emerging
evidence
suggests
that
ferroptosis,
an
iron-dependent
form
regulated
cell
death
driven
lipid
peroxidation
oxidative
stress,
plays
significant
role
in
its
pathogenesis.
Ferroptotic
stress
not
only
compromises
epithelial
integrity,
but
also
triggers
inflammatory
responses
profibrotic
signaling
cascades
activate
sustain
fibroblast
dysfunction.
This
review
delineates
core
regulatory
pathways
iron
metabolism,
peroxidation,
antioxidant
defenses,
mitochondrial
remodeling,
RNA
editing,
with
emphasis
on
their
relevance
IPF.
We
explore
how
injury
macrophage-derived
signals
initiate
subsets,
shaped
scRNA-seq-defined
heterogeneity
plasticity,
respond
to
these
cues
reinforcing
ECM
deposition
stress.
Therapeutic
avenues
targeting
including
supplementation,
chelation,
modulation
are
discussed
alongside
cell-specific
interventions
nanodelivery
strategies.
By
integrating
recent
advances
molecular
profiling
ferroptosis
biology,
this
provides
framework
for
leveraging
as
tractable
target
identifies
novel
directions
precision
antifibrotic
therapy.
Язык: Английский
Promoting Ferroptosis of Keloid Fibroblasts: A Key Mechanism Underlying the Efficacy of 5-Aminolevulinic Acid Photodynamic Therapy for Keloids
Опубликована: Янв. 1, 2025
Язык: Английский
Skin Aging and the Upcoming Role of Ferroptosis in Geroscience
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(15), С. 8238 - 8238
Опубликована: Июль 28, 2024
The
skin
is
considered
the
most
important
organ
system
in
mammals,
and
as
population
ages,
it
to
consider
aging
anti-aging
therapeutic
strategies.
Exposure
of
various
insults
induces
significant
changes
throughout
our
lives,
differentiating
a
young
adult
from
that
an
older
adult.
These
are
caused
by
combination
intrinsic
extrinsic
aging.
We
report
interactions
between
its
metabolism,
showing
network
due
several
factors.
For
example,
iron
nutrient
for
humans,
but
level
increases
with
aging,
inducing
deleterious
effects
on
cellular
functions.
Recently,
was
discovered
ferroptosis,
or
iron-dependent
cell
death,
linked
diseases.
pursuit
new
molecular
targets
ferroptosis
has
recently
attracted
attention.
Prevention
effective
strategy
treatment
diseases,
especially
old
age.
However,
pathological
biological
mechanisms
underlying
still
not
fully
understood,
diseases
such
melanoma
autoimmune
Only
few
basic
studies
regulated
death
exist,
challenge
turn
into
clinical
applications.
Язык: Английский
Increased melanin induces aberrant keratinocyte−melanocyte−basal−fibroblast cell communication and fibrogenesis by inducing iron overload and ferroptosis resistance in keloids
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 15, 2024
Abstract
Keloid
is
a
typical
skin
fibrotic
disease
with
unclear
mechanisms
and
limited
therapeutic
options.
In
this
study,
we
found
the
enriched
pigmentation-related
pathways
in
melanocytes
of
keloid
by
single-cell
RNA-sequence
(scRNA-seq)
analysis.
We
further
validated
increased
melanin
levels
patients.
Additionally,
positively
correlated
Area
Severity
Index
keloid.
Furthermore,
melanocyte-secreted
significantly
promoted
fibroblast
proliferation,
migration,
collagen
synthesis.
Mechanically,
basal
cell
permeability
inflammation
to
facilitate
its
transfer
dermis,
where
it
activated
fibroblasts
evoking
iron
overload
ferroptosis
resistance.
Consistently,
resistance
were
primary
tissues
Inhibition
effectively
diminish
melanin-induced
fibrogenesis.
Interestingly,
induced
an
autocrine
manner
stimulated
keratinocytes
take
up
deepen
color
upregulating
F2R-like
trypsin
receptor
1
(F2RL1).
In
vivo,
delivery
ML329,
micropthalmia-associated
transcription
factor
(MITF)
inhibitor,
could
suppress
melanogenesis
alleviate
human
keloid-bearing
nude
mice.
Meanwhile,
ML329
decreased
content
restored
sensitivities
ferroptosis.
Collectively,
melanin-lowing
strategies
may
appear
as
potential
new
target
for
Язык: Английский
Unveiling ferroptosis: a new frontier in skin disease research
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 4, 2024
Ferroptosis,
a
form
of
regulated
cell
death
distinct
from
apoptosis,
necrosis,
and
autophagy,
is
increasingly
recognized
for
its
role
in
skin
disease
pathology.
Characterized
by
iron
accumulation
lipid
peroxidation,
ferroptosis
has
been
implicated
the
progression
various
conditions,
including
psoriasis,
photosensitive
dermatitis,
melanoma.
This
review
provides
an
in-depth
analysis
molecular
mechanisms
underlying
compares
cellular
effects
with
other
forms
context
health
disease.
We
systematically
examine
five
specific
diseases,
ichthyosis,
polymorphous
light
eruption
(PMLE),
vitiligo,
melanoma,
detailing
influence
on
pathogenesis
progression.
Moreover,
we
explore
current
clinical
landscape
ferroptosis-targeted
therapies,
discussing
their
potential
managing
treating
diseases.
Our
aim
to
shed
therapeutic
modulating
research
practice.
Язык: Английский