Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: June 7, 2024
Pyruvate
kinase
M2
(PKM2),
a
rate
limiting
enzyme
in
glycolysis,
is
cellular
regulator
that
has
received
extensive
attention
and
regards
as
metabolic
of
metabolism
energy.
Kidney
highly
metabolically
active
organ,
glycolysis
the
important
energy
resource
for
kidney.
The
accumulated
evidences
indicates
enzymatic
activity
PKM2
disturbed
kidney
disease
progression
treatment,
especially
diabetic
acute
injury.
Modulating
post-translational
modification
determines
its
nuclear
translocation
serves
an
interventional
approach
to
regulate
PKM2.
Emerging
show
participate
treatment
through
modulating
regulation,
podocyte
injury,
fibroblast
activation
proliferation,
macrophage
polarization,
T
cell
regulation.
Interestingly,
activators
(TEPP-46,
DASA-58,
mitapivat,
TP-1454)
inhibitors
(shikonin,
alkannin,
compound
3k
3h)
have
exhibited
potential
therapeutic
property
disease,
which
pleiotropic
effects
In
future,
deep
investigation
urgently
needed
determine
effect
activator/inhibitor
benefit
patients.
information
this
review
highlights
functions
biomarker
target
diseases.
BMC Biology,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Dec. 31, 2024
Age-related
kidney
impairment,
characterized
by
tubular
epithelial
cell
senescence
and
renal
fibrosis,
poses
a
significant
global
public
health
threat.
Although
N6-methyladenosine
(m6A)
methylation
is
implicated
in
various
pathological
processes,
its
regulatory
mechanism
aging
remains
unclear.
An
m6A-mRNA
epitranscriptomic
microarray
was
performed
to
identify
genes
with
abnormal
m6A
modifications
aged
human
tissues.
Histological,
immunohistochemical,
immunofluorescent
staining,
western
blot,
RT-qPCR
were
employed
examine
the
biological
functions
of
targeted
methyltransferases
both
vivo
vitro.
RNA
immunoprecipitation,
chromatin
ribosomal
luciferase
reporter
assays
used
investigate
specific
interactions
between
methyltransferases,
genes,
their
downstream
signals.
Significantly
lower
modification
levels
observed
GLIS1,
identified
as
"metabolic
remodeling
factor,"
showed
significantly
reduced
protein
modifications.
The
downregulation
GLIS1
induced
fibrosis
shifting
metabolic
from
fatty
acid
oxidation
(FAO)
glycolysis.
Additionally,
methylated
mRNA
regulated
expression
METTL3
YTHDF1.
Silencing
METTL3/YTHDF1
weakened
translation
disrupted
balance
FAO
Our
findings
suggest
that
activated
YTHDF1-dependent
manner,
leads
regulating
shift
This
provides
promising
therapeutic
target
for
aging.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 5, 2024
Abstract
Aberrant
mesangial
cell
proliferation
is
a
prevailing
histopathological
feature
of
immunoglobulin
A
nephropathy
(IgAN)
and
the
primary
driver
glomerular
sclerosis
impaired
renal
function
in
IgAN
patients.
Prior
research
has
revealed
that
PKM2-mediated
aerobic
glycolysis
(the
Warburg
effect)
frequently
promotes
growth
contributes
to
development
various
acute
chronic
kidney
diseases.
However,
expression
functionality
PKM2
IgA
nephropathy,
as
well
underlying
molecular
mechanisms
governing
its
abnormal
expression,
remain
elusive.
Circular
RNAs,
subset
noncoding
have
garnered
increasing
attention
due
mounting
evidence
their
pivotal
roles
initiation
progression
numerous
disorders.
The
present
study
aimed
explore
effects
circRNA_0013747
on
potential
mechanisms.
results
indicated
notable
overexpression
lipopolysaccharide
(LPS)-treated
human
cells
(HMCs)
biopsy
samples
from
CircRNA_0013747
was
shown
facilitate
activate
glycolysis,
although
these
were
mitigated
by
an
increase
miR-330-3p.
Mechanistically,
physically
interacted
with
microRNA-330-3p
(miR-330-3p)
hindered
directly
binding
it.
These
findings
imply
can
enhance
modulating
miR-330-3p/PKM2
signaling
pathway.
In
conclusion,
underscore
possibility
serving
promising
therapeutic
target
for
IgAN,
suggesting
new
prospects
treating
this
disease.
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Nov. 21, 2024
A
significant
research
gap
exists
regarding
the
role
of
tissue
exosomes
in
intrauterine
adhesions
(IUAs).
This
study
aims
to
investigate
involvement
miR-195-5p
and
its
regulatory
network
IUAs
through
analysis
exosomes.
Exosomes
from
rat
uterine
with
were
analyzed
via
transcriptomics
identify
downstream
target
genes
miR-195-5p,
cross-referencing
human
endometrial
database
GSE224093.
Dual
luciferase
labeling
confirmed
miRNA-target
gene
interactions.
The
therapeutic
efficacy
a
agonist
was
assessed
vivo
HE
staining,
Masson
mating
tests.
mechanisms
underlying
extracellular
matrix
(ECM)
deposition
myofibroblast
transdifferentiation
fibrosis
investigated
both
vitro
using
RT-PCR,
Western
Blot,
immunofluorescence,
immunohistochemistry.
Migration
ability
stromal
cells
evaluated
CCK8,
scratch
tests,
Transwell
assays.
Finally,
clinical
potential
compared
autologous
adipose-derived
mesenchymal
stem
cells.
expression
found
be
decreased.
Treatment
resulted
improved
health,
reduced
fibrosis,
increased
glandular
density,
enhanced
birth
rates
rats.
Both
experiments
that
decreased
ECM
deposition,
transdifferentiation,
inhibited
migration
achieved
downregulation
YAP
Hippo
pathway
upregulation
Smad7.
Notably,
agonists
comparable
cell
therapy,
offering
promising
avenues
for
application.
Differential
can
reduce
improving
by
regulating
YAP-Smad7
signaling
cascade.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Dec. 16, 2024
Kidney
immune
homeostasis
is
intricately
linked
to
T
cells.
Inappropriate
differentiation,
activation,
and
effector
functions
of
cells
lead
a
spectrum
kidney
disease.
While
executing
functions,
undergo
series
metabolic
rewiring
meet
the
rapid
energy
demand.
The
key
enzymes
metabolites
involved
in
cell
metabolism
metabolically
epigenetically
modulate
cells'
thereby
being
capable
modulating
homeostasis.
In
this
review,
we
first
summarize
latest
advancements
immunometabolism.
Second,
outline
alterations
renal
microenvironment
under
certain
disease
conditions.
Ultimately,
highlight
modulation
within
homeostasis,
which
may
shed
light
on
new
strategies
for
treating
