Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 7, 2024
Abstract
Epithelial-to-mesenchymal
transition
(EMT)
is
crucial
for
the
progression
of
renal
tubulointerstitial
fibrosis,
typically
leading
to
end-stage
failure.
The
role
Nuclear
receptor
subfamily
5
group
A
member
2
(NR5A2)
in
fibrosis
not
yet
fully
understood.
This
research
assessed
NR5A2
expression
human
and
mouse
models
with
unilateral
ureteral
obstruction
(UUO).
We
further
investigated
NR5A2's
function
TGF-β1-driven
tubular
EMT.
Our
findings
demonstrated
a
significant
elevation
profibrogenic
agents
like
collagen-I(Col-Ⅰ),
alpha-smooth
muscle
actin
(α-SMA),
fibronectin
(FN)
UUO-induced
model.
Suppressing
blocking
it
ML180
diminished
TGF-β1-induced
E-cadherin,
α-SMA,
Col-Ⅰ
,
FN
HK2
cells.
Functionally,
boosted
MMP25
cells
after
TGF-β1
activation.
Luciferase
Chromatin
Immunoprecipitation
(ChIP)
assays
verified
attachment
distinct
motif
on
promoter,
initiating
transcription.
Crucially,
silencing
countered
NR5A2-induced
factors
following
These
insights
reveal
that
orchestrates
TGF-β1-prompted
EMT
via
MMP25,
highlighting
novel
avenue
curbing
fibrosis.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(9), P. 1942 - 1942
Published: Aug. 23, 2024
Chronic
kidney
disease
(CKD)
is
a
major
global
health
concern.
Renal
fibrosis,
prevalent
outcome
regardless
of
the
initial
cause,
ultimately
leads
to
end-stage
renal
disease.
Glomerulosclerosis
and
interstitial
fibrosis
are
primary
pathological
features.
Preventing
slowing
considered
effective
strategies
for
delaying
CKD
progression.
However,
treatments
lacking.
Sirtuin
1
(SIRT1),
nicotinamide
adenine
dinucleotide
(NAD+)-dependent
deacetylase
belonging
class
III
histone
deacetylases,
implicated
in
physiological
regulation
protection
susceptible
diverse
array
influences,
as
demonstrated
previous
studies.
Interestingly,
controversial
conclusions
have
emerged
research
has
progressed.
This
review
provides
comprehensive
summary
current
understanding
advancements
field;
specifically,
biological
roles
mechanisms
SIRT1
regulating
These
include
aspects
such
lipid
metabolism,
epithelial-mesenchymal
transition,
oxidative
stress,
aging,
inflammation,
autophagy.
manuscript
explores
potential
therapeutic
target
offers
new
perspectives
on
treatment
approaches
prognostic
assessments.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Oct. 2, 2024
Purpose
Rhubarb
(
Rheum
palmatum
L.)
and
astragalus
(Radix
astragali)
find
widespread
used
in
clinical
formulations
for
treating
chronic
kidney
disease
(CKD).
Notably,
the
key
active
components,
total
rhubarb
anthraquinone
(TRA)
saponin
(TAS),
exhibit
superiority
over
terms
of
their
clear
composition,
stability,
quality
control,
small
dosage,
efficacy
treatment.
Additionally,
polysaccharides
(APS)
significantly
contribute
to
treatment
renal
fibrosis
by
modulating
gut
microbiota.
However,
due
differences
biopharmaceutical
properties
these
achieving
synergistic
effects
remains
challenging.
This
study
aims
develop
combined
pellets
(CPs)
evaluate
potential
effect
on
unilateral
ureteral
obstruction
(UUO)-induced
fibrosis.
Methods
The
CPs
were
obtained
combining
TRA/TAS-loaded
SNEDDS
APS-loaded
pellets,
prepared
using
fluidized
bed
coating
process.
underwent
evaluation
morphology,
bulk
density,
hardness,
flowing
property.
Moreover,
vitro
release
payloads
was
evaluated
with
CHP
Type
I
method.
Furthermore,
(UUO)
model
utilized
investigate
contribution
microbiota
modulation.
Results
ex-vivo
demonstrated
that
developed
not
only
improved
dissolution
TRA
TAS
but
also
delivered
TRA/TAS
APS
spatiotemporally
appropriate
site
along
gastrointestinal
tract.
In
an
animal
(UUO
rats),
oral
administration
ameliorated
histological
pathology,
reduced
collagen
deposition,
decreased
levels
inflammatory
cytokines.
restored
disturbed
induced
UUO
surgery
protected
intestinal
barrier.
Conclusion
represent
a
promising
strategy
efficiently
delivering
components
traditional
Chinese
medicine
formulas,
offering
effective
approach
CKD.
AJP Renal Physiology,
Journal Year:
2023,
Volume and Issue:
325(6), P. F826 - F856
Published: Oct. 12, 2023
Fibroblasts
are
integral
to
the
organization
and
function
of
all
organs
play
critical
roles
in
pathologies
such
as
fibrosis;
however,
we
have
limited
understanding
fibroblasts
that
populate
bladder
kidney.
In
this
review,
I
describe
how
transcriptomics
is
leading
a
revolution
our
fibroblast
biology
by
defining
molecular
fingerprint
(i.e.,
transcriptome)
universal
specialized
types,
revealing
gene
signatures
allows
one
resolve
from
other
mesenchymal
cell
providing
new
comprehension
lineage.
kidney,
giving
us
insights
into
kidney
fibroblasts,
including
those
for
cortical
medullary
erythropoietin
(EPO)-producing
Norn
well
information
about
myofibroblasts
transition
myofibroblasts.
Transcriptomics
has
also
revealed
major
type
interstitium
fibroblast,
multiple
each
with
their
own
fingerprint,
found
wall.
Interleaved
throughout
discussion
can
drive
future
identification,
diversity,
function,
physiology
health
disease
states.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 29, 2024
AbstractBackground:
Chronic
Kidney
Disease
(CKD)
impacts
over
10%
of
the
global
population
and
recently
advancements
in
high-throughput
analytical
technologies
are
uncovering
complex
physiology
underlying
this
condition.
Through
integration
Genome-Wide
Association
Studies
(GWAS),
RNA
sequencing
(RNA-seq),
single-cell
(scRNA-seq)
summary
statistics,
our
study
aimed
to
explore
genes
cell
types
relevant
CKD
traits.
Methods:
The
GWAS
Catalog
UK
Biobank
(UKB)
database
provided
data
for
end
stage
renal
failure
(ESRD)
decreased
eGFR
with
or
without
diabetes
(micro)proteinuria.
Gene
Expression
Omnibus
(GEO)
transcriptome
datasets
were
utilized
establish
glomerular
tubular
gene
expression
between
patients
healthy
individuals.
The
key
at
level
obtained
from
ScRNA-seq
dataset
available
on
Zenodo.
differentially
expressed
(DEGs),
crosstalk
co-expression
networks,
enrichment
analysis
further
conducted
these
risk
genes.
Results:
A
total
779
distinct
SNPs
identified
across
different
traits
CKDs,
which
involved
681
Majority
identical
referring
certain
trait,
but
share
common
pathways,
including
extracellular
matrix
(ECM),
circadian
entrainment,
energy
metabolism.
ECM
modelling
was
also
enriched
upregulated
DEGs
kidneys
compared
controls
collagen
genes,
COL8A1,
COL6A3,
COL1A2,
prevalent
fibroblasts/myofibroblasts.
Meanwhile,
physiological
functions
kidney,
downregulated
kidneys.
LUC7L3
podocytes.
We
highlighted
regulated
mainly
cells
immune
kidney.
Conclusions:
Our
integrated
highlight
associational
pathogenesis
kidney
traits,
as
a
basis
mechanistic
studies
understand
CKD.
Journal of Biochemical and Molecular Toxicology,
Journal Year:
2024,
Volume and Issue:
38(8)
Published: Aug. 1, 2024
Renal
fibrosis
(RF)
is
one
of
the
underlying
pathological
conditions
leading
to
progressive
loss
renal
function
and
end-stage
disease
(ESRD).
Over
years,
various
therapeutic
approaches
have
been
explored
combat
RF
prevent
ESRD.
Despite
significant
advances
in
understanding
molecular
mechanism(s),
effective
interventions
for
are
limited.
Current
strategies
primarily
target
these
mechanisms
halt
or
reverse
fibrotic
progression.
Inhibition
transforming
growth
factor-β
(TGF-β)
signaling,
a
pivotal
mediator
has
emerged
as
central
strategy
manage
RF.
Small
molecules,
peptides,
monoclonal
antibodies
that
TGF-β
receptors
downstream
effectors
demonstrated
potential
preclinical
models.
Modulating
renin-angiotensin
system
targeting
endothelin
also
provide
established
controlling
fibrosis-related
hemodynamic
changes.
Complementary
pharmacological
strategies,
lifestyle
modifications,
dietary
contribute
holistic
management.
This
comprehensive
review
aims
summarize
an
overview
novel
antifibrotic
agents
hold
promise
its
treatment.
