Cell Reports,
Год журнала:
2023,
Номер
42(12), С. 113431 - 113431
Опубликована: Ноя. 30, 2023
In
autosomal
dominant
polycystic
kidney
disease
(ADPKD),
renal
cyst
lesions
predominantly
arise
from
collecting
ducts
(CDs).
However,
relevant
CD
models
using
human
cells
are
lacking.
Although
previous
reports
have
generated
in
vitro
tubule
induced
pluripotent
stem
(hiPSCs),
therapeutic
drug
candidates
for
ADPKD
not
been
identified.
Here,
by
establishing
expansion
cultures
of
hiPSC-derived
ureteric
bud
tip
cells,
an
embryonic
precursor
that
gives
rise
to
CDs,
we
succeed
advancing
the
developmental
stage
organoids
and
show
all
derived
PKD1−/−
hiPSCs
spontaneously
develop
multiple
cysts,
clarifying
initiation
mechanisms
cystogenesis.
Moreover,
identify
retinoic
acid
receptor
(RAR)
agonists
as
candidate
drugs
suppress
cystogenesis
confirm
effects
on
mouse
model
vivo.
Therefore,
our
contributes
understanding
discovery
ADPKD.
Journal of the American Society of Nephrology,
Год журнала:
2023,
Номер
34(9), С. 1480 - 1491
Опубликована: Июнь 21, 2023
Fetal
kidney
development
is
characterized
by
increased
uptake
of
glucose,
ATP
production
glycolysis,
and
upregulation
mammalian
target
rapamycin
(mTOR)
hypoxia-inducible
factor-1
alpha
(HIF-1
α
),
which
(acting
in
concert)
promote
nephrogenesis
a
hypoxic
low-tubular-workload
environment.
By
contrast,
the
healthy
adult
sirtuin-1
adenosine
monophosphate-activated
protein
kinase,
enhances
through
fatty
acid
oxidation
to
fulfill
needs
normoxic
high-tubular-workload
During
stress
or
injury,
reverts
fetal
signaling
program,
adaptive
short
term,
but
deleterious
if
sustained
for
prolonged
periods
when
both
oxygen
tension
tubular
workload
are
heightened.
Prolonged
increases
glucose
glomerular
proximal
cells
lead
enhanced
flux
hexosamine
biosynthesis
pathway;
its
end
product-uridine
diphosphate
N
-acetylglucosamine-drives
rapid
reversible
O-GlcNAcylation
thousands
intracellular
proteins,
typically
those
that
not
membrane-bound
secreted.
Both
phosphorylation
act
at
serine/threonine
residues,
whereas
regulated
hundreds
specific
kinases
phosphatases,
only
O-GlcNAc
transferase
O-GlcNAcase,
adds
removes
N-acetylglucosamine,
respectively,
from
proteins.
Diabetic
nondiabetic
CKD
reprogramming
(with
mTOR
HIF-1
)
O-GlcNAcylation,
experimentally
clinically.
Augmentation
oxidative
stress,
cell
cycle
entry,
apoptosis,
activation
proinflammatory
profibrotic
pathways,
it
inhibits
megalin-mediated
albumin
endocytosis
mesangial
cells-effects
can
be
aggravated
attenuated
augmentation
muting
respectively.
In
addition,
drugs
with
known
nephroprotective
effects-angiotensin
receptor
blockers,
mineralocorticoid
antagonists,
sodium-glucose
cotransporter
2
inhibitors-are
accompanied
diminished
kidney,
although
role
such
suppression
mediating
their
benefits
has
been
explored.
The
available
evidence
supports
further
work
on
uridine
-acetylglucosamine
as
critical
nutrient
surplus
sensor
concert
upregulated
signaling)
diabetic
CKD.
Poultry Science,
Год журнала:
2024,
Номер
103(7), С. 103774 - 103774
Опубликована: Апрель 18, 2024
Goose
astrovirus
genotype
2
(GAstV-2)
mainly
causes
gout
in
goslings;
therefore,
it
is
a
major
pathogen
threatening
to
goose
flocks.
However,
the
mechanisms
underlying
host-GAstV-2
interactions
remain
unclear
because
host
cells
suitable
for
GAstV-2
replication
have
been
unavailable.
We
previously
noted
that
primarily
located
renal
epithelial
cells,
where
kidney
damage.
Therefore,
here,
we
derived
primary
tubular
(RTE)
(GRTE
cells)
from
kidneys
of
embryos
after
collagenase
I
digestion.
After
culture
Dulbecco's
modified
Eagle
medium/Nutrient
mixture
F-12
with
10%
fetal
bovine
serum
(FBS),
isolated
had
polygonal
roadstone-like
morphology;
they
were
identified
be
based
on
presence
cytokeratin
18
expression
detected
through
immunofluorescence
assay
(IFA).
infection
GRTE
led
no
obvious
cytopathic
effects;
maximum
amounts
infectious
virions
observed
48
h
post
IFA
and
quantitative
PCR.
Next,
RNA-seq
was
performed
identify
map
post–GAstV-2
differentially
expressed
genes.
The
downregulated
pathways
related
metabolism,
including
tryptophan
drug
metabolism
by
cytochrome
P450,
xenobiotic
retinol
butanoate
starch
sucrose
ascorbate
aldarate
other
enzymes
peroxisome.
In
contrast,
upregulated
mostly
cell
defense
proliferation,
extracellular
matrix–receptor
interaction,
complement
coagulation
cascades,
phagosome,
PI3K-Akt
signaling
pathway,
human
T-lymphotropic
virus
1
infection,
lysosome,
tumor
necrosis
factor
pathway.
conclusion,
developed
line
analyzed
potential
host–GAstV-2
RNA-seq;
our
results
may
aid
further
investigating
pathogenic
provide
strategies
its
prevention
control.
Cell Reports,
Год журнала:
2023,
Номер
42(12), С. 113431 - 113431
Опубликована: Ноя. 30, 2023
In
autosomal
dominant
polycystic
kidney
disease
(ADPKD),
renal
cyst
lesions
predominantly
arise
from
collecting
ducts
(CDs).
However,
relevant
CD
models
using
human
cells
are
lacking.
Although
previous
reports
have
generated
in
vitro
tubule
induced
pluripotent
stem
(hiPSCs),
therapeutic
drug
candidates
for
ADPKD
not
been
identified.
Here,
by
establishing
expansion
cultures
of
hiPSC-derived
ureteric
bud
tip
cells,
an
embryonic
precursor
that
gives
rise
to
CDs,
we
succeed
advancing
the
developmental
stage
organoids
and
show
all
derived
PKD1−/−
hiPSCs
spontaneously
develop
multiple
cysts,
clarifying
initiation
mechanisms
cystogenesis.
Moreover,
identify
retinoic
acid
receptor
(RAR)
agonists
as
candidate
drugs
suppress
cystogenesis
confirm
effects
on
mouse
model
vivo.
Therefore,
our
contributes
understanding
discovery
ADPKD.
