Hypoxia causes trophoblast cell ferroptosis to induce miscarriage through lnc-HZ06/HIF1α-SUMO/NCOA4 axis
Redox Biology,
Год журнала:
2024,
Номер
70, С. 103073 - 103073
Опубликована: Фев. 2, 2024
Defects
of
human
trophoblast
cells
may
induce
miscarriage
(abnormal
early
embryo
loss),
which
is
generally
regulated
by
lncRNAs.
Ferroptosis
a
newly
identified
iron-dependent
programmed
cell
death.
Hypoxia
an
important
and
unavoidable
feature
in
mammalian
cells.
However,
whether
hypoxia
might
ferroptosis
then
miscarriage,
as
well
lncRNA,
was
completely
unknown.
In
this
work,
we
discovered
at
the
first
time
that
could
result
miscarriage.
We
also
novel
lncRNA
(lnc-HZ06)
simultaneously
(indicated
HIF1α
protein),
ferroptosis,
mechanism,
HIF1α-SUMO,
instead
itself,
primarily
acted
transcription
factor
to
promote
NCOA4
(ferroptosis
indicator)
hypoxic
Lnc-HZ06
promoted
SUMOylation
suppressing
SENP1-mediated
deSUMOylation.
HIF1α-SUMO
lnc-HZ06
transcription.
Thus,
both
formed
positive
auto-regulatory
feedback
loop.
This
loop
up-regulated
cells,
RM
villous
tissues,
placental
tissues
hypoxia-treated
mice,
further
induced
up-regulating
HIF1α-SUMO-mediated
Furthermore,
knockdown
either
murine
lnc-hz06
or
Ncoa4
efficiently
suppress
alleviate
mouse
model.
Taken
together,
study
provided
new
insights
understanding
regulatory
roles
lnc-HZ06/HIF1α-SUMO/NCOA4
axis
among
hypoxia,
offered
effective
approach
for
treatment
against
Язык: Английский
Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage
Advanced Science,
Год журнала:
2024,
Номер
11(13)
Опубликована: Янв. 29, 2024
Abstract
Human
trophoblast
cells
are
crucial
for
healthy
pregnancy.
However,
whether
the
defective
homologous
recombination
(HR)
repair
of
dsDNA
break
(DSB)
in
may
induce
miscarriage
is
completely
unknown.
Moreover,
abundance
BRCA1
(a
protein
HR
repair),
its
recruitment
to
DSB
foci,
and
epigenetic
regulatory
mechanisms,
also
fully
unexplored.
In
this
work,
it
identified
that
a
novel
lnc‐HZ10,
which
highly
experssed
villous
tissues
recurrent
(RM)
vs
their
control
group,
suppresses
cell.
Lnc‐HZ10
AhR
(aryl
hydrocarbon
receptor)
form
positive
feedback
loop.
acts
as
transcription
factor
promote
lnc‐HZ10
transcription.
Meanwhile,
increases
levels
by
suppressing
CUL4B‐mediated
ubiquitination
degradation.
Subsequently,
transcription;
(mainly
1‐447
nt)
interacts
with
γ‐H2AX;
thus,
impairs
interactions
BRCA1.
BPDE
exposure
trigger
loop
suppress
cells,
possibly
inducing
miscarriage.
Knockdown
murine
Ahr
efficiently
recovers
placental
alleviates
mouse
model.
Therefore,
suggested
AhR/lnc‐HZ10/BRCA1
axis
be
promising
target
alleviation
unexplained
Язык: Английский
BaP/BPDE suppresses human trophoblast cell migration/invasion and induces unexplained miscarriage by up-regulating a novel lnc-HZ11 in extracellular vesicles: An intercellular study
Environment International,
Год журнала:
2024,
Номер
188, С. 108750 - 108750
Опубликована: Май 21, 2024
Extracellular
vesicles
(EVs)
mediate
the
intercellular
crosstalk
by
transferring
functional
cargoes.
Recently,
we
have
discovered
that
BaP/BPDE
exposure
suppresses
trophoblast
cell
migration/invasion
and
induces
miscarriage,
which
are
also
regulate
lncRNAs
at
intracelluar
levels.
However,
EVs-mediated
regulatory
mechanisms
completely
unexplored.
Specifically,
whether
EVs
might
transfer
BPDE-induced
toxic
lncRNA
to
fresh
recipient
cells
suppress
their
further
induce
miscarriage
is
unknown.
In
this
study,
find
BPDE
up-regulates
a
novel
lnc-HZ11,
EGR1/NF-κB/CXCL12
pathway
of
cells.
Intercellular
studies
show
EV-HZ11
(lnc-HZ11
in
EVs),
highly
expressed
BPDE-exposed
donor
cells,
lnc-HZ11
through
EVs.
Analysis
villous
tissues
collected
from
UM
(unexplained
miscarriage)
patients
HC
(healthy
control)
group
shows
levels
BPDE-DNA
adducts,
or
EV-lnc-HZ11,
all
associated
with
miscarriage.
Mouse
assays
BaP
lnc-Hz11
EV-Hz11,
Egr1/Nf-κb/Cxcl12
pathway,
eventually
Knockdown
injecting
EV-AS-Hz11
could
effectively
alleviate
BaP-exposed
mice.
Furthermore,
serum
samples
well
predict
risk
Collectively,
study
not
only
discovers
EVs-HZ11-mediated
but
provides
new
approach
for
treatment
against
unexplained
EV-HZ11.
Язык: Английский
BaP/BPDE exposure causes human trophoblast cell dysfunctions and induces miscarriage by up-regulating lnc-HZ06-regulated IL1B
Journal of Hazardous Materials,
Год журнала:
2024,
Номер
476, С. 134741 - 134741
Опубликована: Июнь 12, 2024
Язык: Английский
Lnc-HZ06 down-regulates HIF1α protein levels in CoCl2-exposed hypoxic trophoblast cells and villous tissues of miscarriage patients
The Science of The Total Environment,
Год журнала:
2025,
Номер
978, С. 179477 - 179477
Опубликована: Апрель 21, 2025
Язык: Английский
Organ-specific lithium accumulation and its toxic effects on female reproduction
Journal of Hazardous Materials,
Год журнала:
2025,
Номер
unknown, С. 138516 - 138516
Опубликована: Май 1, 2025
Язык: Английский
BaP/BPDE suppresses homologous recombination repair in human trophoblast cells to induce miscarriage: The roles of lnc-HZ08
Environment International,
Год журнала:
2024,
Номер
191, С. 108975 - 108975
Опубликована: Авг. 24, 2024
Benzo(a)pyrene
(BaP)
or
benzo
(a)
pyrene
7,8-dihydrodiol-9,10-epoxide
(BPDE)
exposure
causes
trophoblast
cell
dysfunctions
and
induces
miscarriage,
which
is
generally
epigenetically
regulated.
Homologous
recombination
(HR)
repair
of
DNA
double
strand
break
(DSB)
plays
a
crucial
role
in
maintenance
genetic
stability
normal
functions.
However,
whether
BaP/BPDE
might
suppress
HR
human
cells
to
induce
as
well
its
epigenetic
regulatory
mechanism,
largely
unclear.
In
this
study,
we
find
that
suppresses
DSB
eventually
miscarriage
by
up-regulating
lnc-HZ08.
lnc-HZ08
(1)
down-regulates
the
expression
levels
FOXA1
(forkhead
box
A1)
thus
FOXA1-mediated
mRNA
transcription
BRCA1
(Breast
cancer
susceptibility
gene
1)
CtIP
(CtBP-interacting
protein),
(2)
impairs
protein
interactions
competitive
binding
with
through
lnc-HZ08-1
fragment,
also
(3)
BRCA1-mediated
ubiquitination
without
affecting
stability,
three
cells.
Supplement
murine
Ctip
could
efficiently
restore
(i.e.
increase)
alleviate
BaP-exposed
mouse
model.
Collectively,
study
not
only
reveals
association
causality
among
exposure,
defective
repair,
but
discovers
novel
mechanism
lnc-HZ08-regulated
BRCA1/CtIP-mediated
bridging
regulation
instability
providing
an
efficient
approach
for
treatment
against
BaP/BPDE-induced
unexplained
miscarriage.
Язык: Английский
Self-assembled carrier-free formulations based on medicinal and food active ingredients
Biomaterials Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
The
popularity
of
medicinal
plants,
which
have
a
unique
system
and
are
mostly
used
in
compound
form
for
the
prevention
treatment
wide
range
diseases,
is
growing
worldwide.
In
recent
years,
with
advances
chemical
separation
structural
analysis
techniques,
many
major
bioactive
molecules
plants
been
identified.
However,
active
ingredients
often
possess
characteristics,
including
poor
water
solubility,
stability
bioavailability,
limit
their
therapeutic
applications.
To
address
this
problem,
self-assembly
small
from
food
sources
provides
new
strategy.
Driven
by
various
types
acting
forces,
modifiable
groups,
multiple
sites
action,
hydrophobic
side
chains,
rigid
backbones
properties
able
to
supramolecular
network
hydrogels,
nanoparticles,
micelles,
other
self-assemblies.
This
review
first
summarizes
forms
self-assemblies
such
as
micelles
at
level
action
site,
discusses
studies
on
that
can
be
self-assembly,
addition
summarizing
advantages
variety
disease
applications,
wound
healing,
antitumor,
anticancer,
diabetes
mellitus.
Finally,
problems
self-assemblers
possible
directions
future
development
presented.
We
firmly
believe
potential
develop
effective
compounds
drug-food
homologous
providing
valuable
information
drug
research
strategies
perspectives
modernization
Chinese
medicine.
Язык: Английский