Single-cell atlas reveals multi-faced responses of losartan on tubular mitochondria in diabetic kidney disease
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 21, 2025
Mitochondria
are
crucial
to
the
function
of
renal
tubular
cells,
and
their
dynamic
perturbation
in
many
aspects
is
an
important
mechanism
diabetic
kidney
disease
(DKD).
Single-nucleus
RNA
sequencing
(snRNA-seq)
technology
a
high-throughput
analysis
technique
for
at
level
single
cell
nucleus.
Here,
our
DKD
mouse
single-cell
conveys
more
comprehensive
mitochondrial
profile,
which
helps
us
further
understand
therapeutic
response
this
unique
organelle
family
drugs.
After
high
fat
diet
(HFD),
mice
were
intraperitoneally
injected
with
streptozotocin
(STZ)
induce
DKD,
then
divided
into
three
subsets:
CON
(healthy)
subset,
(vehicle)
LST
(losartan;
25
mg/kg/day)
subset.
Divide
HK-2
LG
(low
glucose;
5
mM)
HG
(high
30
+
1
µ
M)
subsets.
snRNA-seq
was
performed
on
tissues
subset
mice.
To
reveal
effects
losartan
gene
pathway
changes
mitochondria,
Gene
Ontology
(GO)
enrichment
GSEA/GSVA
scoring
analyze
specific
proximal
(PT)
mitochondria
treatment,
including
key
events
homeostasis
such
as
morphology,
dynamics,
mitophagy,
autophagic
flux,
respiratory
chain,
apoptosis,
ROS
generation.
Preliminary
validation
through
vitro
vivo
experiments,
observation
morphology
dynamics
using
probes
Mitotracker
Red,
evaluation
effect
electron
microscopy,
laser
confocal
immunofluorescence,
Western
blotting.
Detection
flux
cells
by
transfecting
Ad-mCherry-GFP-LC3B
dual
fluorescence
labeled
adenovirus.
Various
fluorescent
energy
detector
used
detect
ROS,
respiration
mitochondrion.
Through
atlas
kidneys,
it
found
that
treatment
significantly
increased
percentage
PT
cells.
differentially
expressed
genes
showed
autophagy
mitochondrion
pathway.
Further
GSEA
GSVA
revealed
mitophagy
other
events,
production,
membrane
potential,
adenosine
triphosphate
(ATP)
synthesis,
involved
protective
thereby
improving
homeostasis.
Consistent
results
also
obtained
cellular
experiments.
In
addition,
we
highlighted
subpopulation
phenotype
data,
preliminarily
validated
co-localization
expression
Pink1
Gclc
specimens
patients
treated
losartan.
Our
research
suggests
scRNA-seq
can
reflect
multifaceted
landscape
after
drug
these
findings
may
provide
new
targets
therapy
level.
Язык: Английский
Tangshenning Formula Alleviates Tubular Injury in Diabetic Kidney Disease via the Sestrin2/AMPK/PGC-1α Axis: Restoration of Mitochondrial Function and Inhibition of Ferroptosis
Journal of Ethnopharmacology,
Год журнала:
2025,
Номер
345, С. 119579 - 119579
Опубликована: Март 3, 2025
Язык: Английский
O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modification: Emerging pathogenesis and a therapeutic target of diabetic nephropathy
Diabetic Medicine,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
Abstract
Aims
O‐Linked
β‐N‐acetylglucosamine
(O‐GlcNAc)
modification,
a
unique
post‐translational
modification
of
proteins,
is
elevated
in
diabetic
nephropathy.
This
review
aims
to
summarize
the
current
knowledge
on
mechanisms
by
which
O‐GlcNAcylation
proteins
contributes
pathogenesis
and
progression
nephropathy,
as
well
therapeutic
potential
targeting
O‐GlcNAc
for
its
treatment.
Methods
Current
evidence
literature
was
reviewed
synthesized
narrative
review.
Results
Hyperglycemia
increases
glucose
flux
into
hexosamine
biosynthesis
pathway,
activates
glucosamino‐fructose
aminotransferase
expression
activity,
leading
production
substrate
UDP‐GlcNAc
an
increase
protein
kidney
cells.
Protein
regulates
function
cells
including
mesangial
cells,
podocytes,
proximal
tubular
promotes
renal
interstitial
fibrosis,
resulting
damage.
treatments
such
sodium‐glucose
cotransporter
2
(SGLT‐2)
inhibitors
renin–angiotensin–aldosterone
system
(RAAS)
inhibitors,
delay
disease
progression,
suppress
O‐GlcNAcylation.
Conclusions
Increased
mediates
cell
damage
Although
full
significance
inhibition
not
yet
understood,
it
may
represent
novel
target
treating
Язык: Английский