Experimental Cell Research,
Journal Year:
2020,
Volume and Issue:
392(2), P. 112007 - 112007
Published: April 18, 2020
The
kidney
injury
induced
by
ischemia-reperfusion
(IR)
usually
comes
with
irreversible
renal
fibrosis,
a
process
that
develops
into
chronic
disease
(CKD),
but
the
underlying
cellular
mechanism
has
yet
to
be
determined.
To
test
our
hypothesis
exosomes
are
tightly
connected
fibrosis
following
AKI,
we
studied
role
of
and
transfer
specific
miRNA
among
other
genetic
components
in
injured
tubular
epithelial
cells
(TECs).
We
utilized
an
experimental
IR
mice
model
simulate
fibrotic
environment
tissue
detect
production
exosomes,
found
exosome
deficiency
could
significantly
alleviate
degree
administration.
MiRNA
profiling
extracted
from
samples
or
without
(IRI)
revealed
miR-150
was
markedly
increased
as
compelling
profibrotic
molecule,
evidenced
fact
overexpression
facilitated
fibrosis.
Exosomes
isolated
hypoxia
TECs
also
miR-150.
In
cocultured
fibroblasts
TECs-derived
confirmed
direct
uptake
exosomal
fibroblasts.
Finally,
verified
vivo
ischemia
pretreated
enriched
developed
more
manifestations.
Thus,
current
study
indicated
have
ability
employ
initiate
activation
proliferation
via
shuttling
miR-150-containing
during
reparative
responses,
exosome/miR-150
provides
groundwork
for
research
develop
personalized
therapeutic
approaches
controlling
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: March 17, 2023
Abstract
Chronic
kidney
disease
(CKD)
is
estimated
to
affect
10–14%
of
global
population.
Kidney
fibrosis,
characterized
by
excessive
extracellular
matrix
deposition
leading
scarring,
a
hallmark
manifestation
in
different
progressive
CKD;
However,
at
present
no
antifibrotic
therapies
against
CKD
exist.
fibrosis
identified
tubule
atrophy,
interstitial
chronic
inflammation
and
fibrogenesis,
glomerulosclerosis,
vascular
rarefaction.
Fibrotic
niche,
where
organ
initiates,
complex
interplay
between
injured
parenchyma
(like
tubular
cells)
multiple
non-parenchymal
cell
lineages
(immune
mesenchymal
located
spatially
within
scarring
areas.
Although
the
mechanisms
are
complicated
due
kinds
cells
involved,
with
help
single-cell
technology,
many
key
questions
have
been
explored,
such
as
what
kind
renal
tubules
profibrotic,
myofibroblasts
originate,
which
immune
how
communicate
each
other.
In
addition,
genetics
epigenetics
deeper
that
regulate
fibrosis.
And
reversible
nature
epigenetic
changes
including
DNA
methylation,
RNA
interference,
chromatin
remodeling,
gives
an
opportunity
stop
or
reverse
therapeutic
strategies.
More
marketed
(e.g.,
RAS
blockage,
SGLT2
inhibitors)
developed
delay
progression
recent
years.
Furthermore,
better
understanding
also
favored
discover
biomarkers
fibrotic
injury.
review,
we
update
advances
mechanism
summarize
novel
treatment
for
CKD.
Aging Cell,
Journal Year:
2019,
Volume and Issue:
18(5)
Published: July 18, 2019
Abstract
Renal
fibrosis
is
the
common
pathological
feature
in
a
variety
of
chronic
kidney
diseases.
Aging
highly
associated
with
progression
renal
fibrosis.
Among
several
determinants,
mitochondrial
dysfunction
plays
an
important
role
aging.
However,
underlying
mechanisms
age‐related
are
not
elucidated.
Herein,
we
found
that
Wnt/β‐catenin
signaling
and
renin–angiotensin
system
(RAS)
activity
were
upregulated
aging
kidneys.
Concomitantly,
mass
functions
impaired
Ectopic
expression
Klotho,
antagonist
endogenous
activity,
abolished
d
‐galactose
(
‐gal)‐induced
accelerated
mouse
model
significantly
protected
by
preserving
diminishing
production
reactive
oxygen
species.
In
established
model,
dickkopf
1,
more
specific
Wnt
inhibitor,
mitochondria‐targeted
antioxidant
mitoquinone
restored
attenuated
tubular
senescence
human
proximal
cell
line
(HKC‐8),
ectopic
Wnt1
decreased
biogenesis
induced
mitochondria,
triggered
cellular
senescence.
Moreover,
‐gal
transduction
signaling,
which
further
activated
angiotensin
type
1
receptor
(AT1),
then
increased
HKC‐8
cells
primary
cultured
cells.
These
effects
inhibited
AT1
blocker
losartan.
results
suggest
inhibition
RAS
could
slow
onset
Taken
together,
our
indicate
Wnt/β‐catenin/RAS
mediates
dysfunction.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: July 31, 2023
Abstract
Cellular
mechanotransduction,
a
critical
regulator
of
numerous
biological
processes,
is
the
conversion
from
mechanical
signals
to
biochemical
regarding
cell
activities
and
metabolism.
Typical
cues
in
organisms
include
hydrostatic
pressure,
fluid
shear
stress,
tensile
force,
extracellular
matrix
stiffness
or
tissue
elasticity,
viscosity.
Mechanotransduction
has
been
expected
trigger
multiple
such
as
embryonic
development,
repair
regeneration.
However,
prolonged
excessive
stimulation
can
result
pathological
multi-organ
fibrosis,
tumorigenesis,
cancer
immunotherapy
resistance.
Although
associations
between
normal
homeostasis
diseases
have
identified,
regulatory
mechanisms
among
different
are
not
yet
comprehensively
illustrated,
no
effective
therapies
currently
available
targeting
cue-related
signaling.
This
review
systematically
summarizes
characteristics
typical
conditions
with
updated
evidence.
The
key
effectors
responding
stimulations
listed,
Piezo
channels,
integrins,
Yes-associated
protein
(YAP)
/transcriptional
coactivator
PDZ-binding
motif
(TAZ),
transient
receptor
potential
vanilloid
4
(TRPV4).
We
also
reviewed
signaling
pathways,
therapeutic
targets
cutting-edge
clinical
applications
related
cues.
Cells,
Journal Year:
2021,
Volume and Issue:
10(4), P. 880 - 880
Published: April 13, 2021
During
aging,
body
adiposity
increases
with
changes
in
the
metabolism
of
lipids
and
their
metabolite
levels.
Considering
lipid
metabolism,
excess
increased
lipotoxicity
leads
to
various
age-related
diseases,
including
cardiovascular
disease,
cancer,
arthritis,
type
2
diabetes,
Alzheimer’s
disease.
However,
multifaceted
nature
complexities
make
it
difficult
delineate
its
exact
mechanism
role
during
aging.
With
advances
genetic
engineering
techniques,
recent
studies
have
demonstrated
that
are
associated
aging
diseases.
Lipid
accumulation
impaired
fatty
acid
utilization
organs
pathophysiological
phenotypes
Changes
adipokine
levels
contribute
by
modulating
systemic
inflammation.
Advances
lipidomic
techniques
identified
profiles
Although
remains
unclear
how
is
regulated
or
metabolites
impact
evidence
suggests
a
dynamic
for
as
active
participants
signaling
pathways
regulators
gene
expression.
This
review
describes
our
understanding
established
findings
approaches.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(2), P. 239 - 239
Published: Jan. 20, 2023
Reducing
oxidative
stress
stands
at
the
center
of
a
prevention
and
control
strategy
for
mitigating
cellular
senescence
aging.
Kidney
disease
is
characterized
by
premature
aging
syndrome,
to
find
modulator
targeting
against
stress,
mitochondrial
dysfunction,
in
kidney
cells
could
be
great
significance
prevent
progression
this
disease.
This
review
focuses
on
pathogenic
mechanisms
related
appearance
damage
dysfunction
In
scenario,
anti-aging
Klotho
protein
plays
crucial
role
modulating
signaling
pathways
involving
manganese-containing
superoxide
dismutase
(Mn-SOD)
transcription
factors
FoxO
Nrf2,
known
antioxidant
systems,
other
function
regulators,
such
as
uncoupling
1
(UCP1),
B-cell
lymphoma-2
(BCL-2),
Wnt/β-catenin,
peroxisome
proliferator-activated
receptor
gamma
coactivator
1-alpha
(PGC-1
alpha),
factor
EB,
(TFEB),
(PPAR-gamma).
Therefore,
postulated
very
promising
new
target
future
therapeutic
strategies
mitochondria
abnormalities,
patients.
Clinical Science,
Journal Year:
2020,
Volume and Issue:
134(20), P. 2681 - 2706
Published: Oct. 1, 2020
Abstract
The
extracellular
matrix
(ECM)
is
a
complex
network
of
macromolecules
surrounding
cells
providing
structural
support
and
stability
to
tissues.
understanding
the
ECM
diverse
roles
it
plays
in
development,
homoeostasis
injury
have
greatly
advanced
last
three
decades.
crucial
for
maintaining
tissue
but
also
many
pathological
conditions
arise
from
aberrant
remodelling
during
ageing.
Ageing
characterised
as
functional
decline
over
time
ultimately
leading
dysfunction,
risk
factor
diseases
including
cardiovascular
disease,
diabetes,
cancer,
dementia,
glaucoma,
chronic
obstructive
pulmonary
disease
(COPD)
fibrosis.
changes
are
recognised
major
driver
cell
responses.
Mesenchymal
aged
show
signs
growth
arrest
resistance
apoptosis,
which
indicative
cellular
senescence.
It
was
recently
postulated
that
senescence
contributes
pathogenesis
fibrotic
heart,
kidney,
liver
lung.
Senescent
negatively
impact
regeneration
while
creating
pro-inflammatory
environment
part
senescence-associated
secretory
phenotype
(SASP)
favouring
progression.
In
this
review,
we
explore
summarise
current
knowledge
around
how
potentially
influences
senescent
diseases.
Lastly,
will
possibility
interventions
ECM–senescence
regulatory
pathways
therapeutic
potential
