Identification of druggable targets in acute kidney injury by proteome- and transcriptome-wide Mendelian randomization and bioinformatics analysis
Biology Direct,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: March 27, 2025
Acute
kidney
injury
(AKI)
remains
a
critical
condition
with
limited
therapeutic
options,
predominantly
managed
by
renal
replacement
therapy.
The
challenge
of
developing
targeted
treatments
persists.
We
integrated
genetic
data
related
to
druggable
proteins
and
gene
expression
AKI
genome-wide
association
study
(GWAS)
findings.
Based
on
multi-omics
Mendelian
randomization
(MR),
we
identified
the
potential
causal
influence
5,883
unique
genes
AKI.
also
performed
using
reverse
MR
external
cohort-based
analysis
verify
robustness
this
relationship.
Expression
patterns
these
targets
were
examined
bulk
transcriptome
single-cell
data.
In
addition,
drug
repurposing
analyses
conducted
explore
existing
medications.
constructed
molecular
interaction
network
interplay
between
known
drugs.
Genetically
predicted
levels
seven
twelve
associated
an
increased
risk
Of
these,
six
(NCF1,
TNFRSF1B,
APEH,
ACADSB,
ADD1,
FAM3B)
prioritized
based
robust
evidence
validated
in
independent
cohorts.
Reverse
showed
one-way
relationship
targets.
These
are
expressed
proximal
tubular
cells,
endothelial
collecting
duct-principal
immune
cells
within
both
AKI-affected
normal
tissues.
Several
promising
opportunities
identified,
such
as
telmisartan-NCF1,
calcitriol-ACADSB,
ethinyl
estradiol-ACADSB.
mapping
pathway
integration
provided
further
insights,
suggesting
strategies
for
combinatorial
therapies.
This
extensive
investigation
several
highlighted
repurposing.
findings
offer
valuable
insights
that
could
shape
future
research
development
treatments.
Language: Английский
Multi-omic studies on the pathogenesis of Sepsis
Hongjie Tong,
No information about this author
Yuhang Zhao,
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Ying Cui
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et al.
Journal of Translational Medicine,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: March 24, 2025
Language: Английский
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et al.
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Journal Year:
2024,
Volume and Issue:
144, P. 113687 - 113687
Published: Nov. 26, 2024
Language: Английский