N6-methyladenosine regulates metabolic remodeling in kidney aging through transcriptional regulator GLIS1
BMC Biology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Дек. 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.
Язык: Английский
LAPTM5
Journal of the American Society of Nephrology,
Год журнала:
2024,
Номер
35(12), С. 1624 - 1626
Опубликована: Окт. 15, 2024
Department
of
Nephrology
and
Medical
Intensive
Care,
Charité
–
Universitätsmedizin
Berlin,
Germany;
Berlin
Institute
Health
at
BIH
Biomedical
Innovation
Academy,
Clinician
Scientist
Program,
Germany
Correspondence:
Dr.
Michael
S.
Balzer,
email:
[email
protected]
See
related
article,
"Lysosomal-Associated
Protein
Transmembrane
5,
Tubular
Senescence,
Progression
CKD,"
on
pages
XXX–XXX.
Язык: Английский