Journal of Cellular Physiology,
Год журнала:
2019,
Номер
235(4), С. 3362 - 3371
Опубликована: Сен. 24, 2019
Abstract
Diabetic
nephropathy
(DN)
is
a
common
clinically
relevant
complication
of
diabetes
that
associated
with
damage
to
the
capillaries,
yet
etiology
this
condition
remains
unclear.
Nuclear
factor‐kappa
B
(NF‐κB)
activation
known
be
DN‐related
inflammation
and
disease
progression.
Recent
work
indicated
microRNAs
are
diagnostic
biomarkers
DN
progression
inflammation
in
DN.
miR‐218
play
key
regulatory
roles
certain
cancers
humans,
while
its
influence
on
pathology
uncertain.
The
present
study,
therefore,
sought
assess
how
influences
both
rat
streptozotocin‐induced
model
as
well
an
vitro
system
which
mouse
podocytes
were
stimulated
high
glucose
levels.
We
found
markedly
downregulated
systems
relative
appropriate
controls,
downregulation
was
IKK‐β
upregulation.
In
model,
overexpressing
sufficient
reduce
renal
injury.
further
determined
podocyte
proliferation
impaired
by
treatment,
leading
apoptotic
death
these
cells,
mimics
able
phenotypes.
Overexpressing
also
significantly
dampened
inflammatory
responses
system,
evidenced
reduced
tumor
necrosis
factor‐α,
interleukin‐6
(IL‐6),
IL‐1β,
MCP‐1
then
confirmed
targeting
messenger
RNA
encoding
using
dual‐luciferase
reporter
assay.
Together,
our
results
provide
clear
evidence
regulate
NF‐κB‐mediated
inflammation,
central
Frontiers in Pharmacology,
Год журнала:
2020,
Номер
11
Опубликована: Март 3, 2020
Diabetic
Nephropathy
(DN)
is
the
most
common
cause
of
End-stage
renal
disease
(ESRD).
Although
various
treatments
and
diagnosis
applications
are
available,
DN
remains
a
clinical
economic
burden.
Recent
findings
showed
that
noncoding
RNAs
(ncRNAs)
play
an
important
role
in
progression,
potentially
can
be
used
as
biomarkers
therapeutic
targets.
NcRNAs
refers
to
RNA
species
do
not
encode
for
any
protein,
known
ncRNAs
microRNAs
(miRNAs),
long
(lncRNAs)
circular
(circRNAs).
Dysregulation
these
was
reported
before
patients
animal
models
DN.
Importantly,
there
some
interactions
between
regulate
crucial
steps
progression.
Here,
we
aimed
discuss
their
with
critical
genes
Elucidating
regulatory
network
will
allow
better
understanding
molecular
mechanisms
how
they
act
new
also
potential
targets
treatment.
Journal of Cellular Physiology,
Год журнала:
2020,
Номер
236(2), С. 1454 - 1468
Опубликована: Июль 21, 2020
Diabetic
nephropathy
(DN)
is
acknowledged
as
a
serious
chronic
complication
of
diabetes
mellitus.
Nevertheless,
its
pathogenesis
complicated
and
unclear.
Thus,
in
this
study,
the
role
miR-27a-3p-prohibitin/TMBIM6
signaling
axis
progression
DN
was
elucidated.
Type
2
diabetic
db/db
mice
high
glucose
(HG)-challenged
HK-2
cells
were
used
vivo
vitro
models.
Our
results
showed
that
miR-27a-3p
upregulated
prohibitin
or
transmembrane
BAX
inhibitor
motif
containing
6
(TMBIM6)
downregulated
kidney
tissues
HG-treated
cells.
Silencing
enhanced
expression
TMBIM6
Inhibition
improved
functional
injury,
evidenced
by
decreased
blood
glucose,
urinary
albumin,
serum
creatinine,
urea
nitrogen
levels.
MiR-27a-3p
silencing
ameliorated
renal
fibrosis,
reflected
reduced
profibrogenic
genes
(e.g.,
transforming
growth
factor
β1,
fibronectin,
collagen
I
III,
α-smooth
muscle
actin).
Furthermore,
inhibition
relieved
mitochondrial
dysfunction
mice,
including
upregulation
membrane
potential,
complex
III
activities,
adenosine
triphosphate,
cytochrome
C,
well
suppressing
reactive
oxygen
species
production.
In
addition,
attenuated
endoplasmic
reticulum
(ER)
stress,
p-IRE1α,
p-eIF2α,
XBP1s,
CHOP.
Mechanically,
we
identified
direct
targets
miR-27a-3p.
protected
from
apoptosis,
extracellular
matrix
accumulation,
dysfunction,
ER
stress
regulating
TMBIM6.
Taken
together,
reveal
regulates
DN,
which
can
be
potential
therapeutic
target.
Journal of Cellular Physiology,
Год журнала:
2019,
Номер
235(4), С. 3362 - 3371
Опубликована: Сен. 24, 2019
Abstract
Diabetic
nephropathy
(DN)
is
a
common
clinically
relevant
complication
of
diabetes
that
associated
with
damage
to
the
capillaries,
yet
etiology
this
condition
remains
unclear.
Nuclear
factor‐kappa
B
(NF‐κB)
activation
known
be
DN‐related
inflammation
and
disease
progression.
Recent
work
indicated
microRNAs
are
diagnostic
biomarkers
DN
progression
inflammation
in
DN.
miR‐218
play
key
regulatory
roles
certain
cancers
humans,
while
its
influence
on
pathology
uncertain.
The
present
study,
therefore,
sought
assess
how
influences
both
rat
streptozotocin‐induced
model
as
well
an
vitro
system
which
mouse
podocytes
were
stimulated
high
glucose
levels.
We
found
markedly
downregulated
systems
relative
appropriate
controls,
downregulation
was
IKK‐β
upregulation.
In
model,
overexpressing
sufficient
reduce
renal
injury.
further
determined
podocyte
proliferation
impaired
by
treatment,
leading
apoptotic
death
these
cells,
mimics
able
phenotypes.
Overexpressing
also
significantly
dampened
inflammatory
responses
system,
evidenced
reduced
tumor
necrosis
factor‐α,
interleukin‐6
(IL‐6),
IL‐1β,
MCP‐1
then
confirmed
targeting
messenger
RNA
encoding
using
dual‐luciferase
reporter
assay.
Together,
our
results
provide
clear
evidence
regulate
NF‐κB‐mediated
inflammation,
central
