Abstract
The
underlying
therapeutic
mechanism
of
renal
tubular
epithelium
repair
diabetic
nephropathy
(DN)
by
bone
marrow-derived
mesenchymal
stem
cells
(BM-MSCs)
has
not
been
fully
elucidated.
Recently,
mitochondria
(Mt)
transfer
was
reported
as
a
novel
action
BM-MSCs
to
rescue
injured
cells.
We
investigated
Mt
from
systemically
administered
proximal
epithelial
(PTECs)
in
streptozotocin
(STZ)-induced
animals.
also
transferred
their
impaired
PTECs
when
co-cultured
vitro
,
which
suppressed
apoptosis
PTECs.
Additionally,
BM-MSC-derived
isolated
enhanced
the
expression
mitochondrial
superoxide
dismutase
2
and
Bcl-2
inhibited
reactive
oxygen
species
(ROS)
production
.
Isolated
nuclear
translocation
PGC-1α
restored
megalin
SGLT2
under
high
glucose
condition
(HG)
Moreover,
directly
injected
capsule
STZ
rats
improved
cellular
morphology
STZ-PTECs,
structure
basement
membrane
brush
border
vivo
This
study
is
first
show
damaged
investigate
mechanisms
potential
effects
DN.
The
tricarboxylic
acid
cycle
(TCA)
is
a
series
of
chemical
reactions
used
in
aerobic
organisms
to
generate
energy
via
the
oxidation
acetylcoenzyme
A
(CoA)
derived
from
carbohydrates,
fatty
acids
and
proteins.
In
eukaryotic
system,
TCA
occurs
completely
mitochondria,
while
intermediates
are
retained
inside
mitochondria
due
their
polarity
hydrophilicity.
Under
cell
stress
conditions,
can
become
disrupted
release
contents,
which
act
as
danger
signals
cytosol.
Of
note,
may
also
leak
dysfunctioning
regulate
cellular
processes.
Increasing
evidence
shows
that
metabolites
substantially
involved
regulation
immune
responses.
this
review,
we
aimed
provide
comprehensive
systematic
overview
molecular
mechanisms
each
intermediate
play
key
roles
regulating
immunity
discuss
its
implication
for
activation
suppression.
Theranostics,
Год журнала:
2019,
Номер
9(6), С. 1698 - 1713
Опубликована: Янв. 1, 2019
Elevated
levels
of
plasma
free
fatty
acid
(FFA)
and
disturbed
mitochondrial
dynamics
play
crucial
roles
in
the
pathogenesis
diabetic
kidney
disease
(DKD).However,
mechanisms
by
which
FFA
leads
to
damage
glomerular
podocytes
DKD
effects
Berberine
(BBR)
on
are
not
fully
understood.Methods:
Using
db/db
mice
model
cultured
mouse
podocytes,
we
investigated
molecular
mechanism
FFA-induced
disturbance
testified
BBR
regulating
dysfunction,
podocyte
apoptosis
glomerulopathy
progression
DKD.Results:
Intragastric
administration
for
8
weeks
significantly
reversed
glucose
lipid
metabolism
disorders,
damage,
basement
membrane
thickening,
mesangial
expansion
glomerulosclerosis.BBR
strongly
inhibited
apoptosis,
increased
reactive
oxygen
species
(ROS)
generation,
fragmentation
dysfunction
both
vivo
vitro.Mechanistically,
could
stabilize
morphology
via
abolishing
palmitic
(PA)-induced
activation
dynamin-related
protein
1
(Drp1).Conclusions:
Our
study
demonstrated
first
time
that
may
have
a
previously
unrecognized
role
protecting
glomerulus
positively
Drp1-mediated
dynamics.It
might
serve
as
novel
therapeutic
drug
treatment
DKD.
Abstract
The
underlying
therapeutic
mechanism
of
renal
tubular
epithelium
repair
diabetic
nephropathy
(DN)
by
bone
marrow-derived
mesenchymal
stem
cells
(BM-MSCs)
has
not
been
fully
elucidated.
Recently,
mitochondria
(Mt)
transfer
was
reported
as
a
novel
action
BM-MSCs
to
rescue
injured
cells.
We
investigated
Mt
from
systemically
administered
proximal
epithelial
(PTECs)
in
streptozotocin
(STZ)-induced
animals.
also
transferred
their
impaired
PTECs
when
co-cultured
vitro
,
which
suppressed
apoptosis
PTECs.
Additionally,
BM-MSC-derived
isolated
enhanced
the
expression
mitochondrial
superoxide
dismutase
2
and
Bcl-2
inhibited
reactive
oxygen
species
(ROS)
production
.
Isolated
nuclear
translocation
PGC-1α
restored
megalin
SGLT2
under
high
glucose
condition
(HG)
Moreover,
directly
injected
capsule
STZ
rats
improved
cellular
morphology
STZ-PTECs,
structure
basement
membrane
brush
border
vivo
This
study
is
first
show
damaged
investigate
mechanisms
potential
effects
DN.