Physiological Reviews,
Journal Year:
2017,
Volume and Issue:
97(4), P. 1235 - 1294
Published: Aug. 10, 2017
Notch
signaling
is
an
evolutionarily
highly
conserved
mechanism,
but
in
contrast
to
pathways
such
as
Wnt,
Sonic
Hedgehog,
and
BMP/TGF-β,
occurs
via
cell-cell
communication,
where
transmembrane
ligands
on
one
cell
activate
receptors
a
juxtaposed
cell.
Originally
discovered
through
mutations
Drosophila
more
than
100
yr
ago,
with
the
first
gene
cloned
30
we
are
still
gaining
new
insights
into
broad
effects
of
organisms
across
metazoan
spectrum
its
requirement
for
normal
development
most
organs
body.
In
this
review,
provide
overview
mechanism
at
molecular
level
discuss
how
pathway,
which
architecturally
quite
simple,
able
engage
control
fates
variety
types.
We
current
understanding
can
become
derailed,
either
by
direct
or
aberrant
regulation,
expanding
diseases
cancers
that
consequence
dysregulation.
Finally,
explore
emerging
field
tissue
homeostasis,
examples
from
skin,
liver,
lung,
intestine,
vasculature.
Nature,
Journal Year:
2023,
Volume and Issue:
619(7970), P. 585 - 594
Published: July 19, 2023
Abstract
Understanding
kidney
disease
relies
on
defining
the
complexity
of
cell
types
and
states,
their
associated
molecular
profiles
interactions
within
tissue
neighbourhoods
1
.
Here
we
applied
multiple
single-cell
single-nucleus
assays
(>400,000
nuclei
or
cells)
spatial
imaging
technologies
to
a
broad
spectrum
healthy
reference
kidneys
(45
donors)
diseased
(48
patients).
This
has
provided
high-resolution
cellular
atlas
51
main
types,
which
include
rare
previously
undescribed
populations.
The
multi-omic
approach
provides
detailed
transcriptomic
profiles,
regulatory
factors
localizations
spanning
entire
kidney.
We
also
define
28
states
across
nephron
segments
interstitium
that
were
altered
in
injury,
encompassing
cycling,
adaptive
(successful
maladaptive
repair),
transitioning
degenerative
states.
Molecular
signatures
permitted
localization
these
injury
using
transcriptomics,
while
large-scale
3D
analysis
(around
1.2
million
neighbourhoods)
corresponding
linkages
active
immune
responses.
These
analyses
defined
biological
pathways
are
relevant
time-course
niches,
including
underlying
epithelial
repair
predicted
with
decline
function.
integrated
multimodal
human
represents
comprehensive
benchmark
neighbourhoods,
outcome-associated
publicly
available
interactive
visualizations.
International Journal of Molecular Sciences,
Journal Year:
2017,
Volume and Issue:
18(10), P. 2157 - 2157
Published: Oct. 17, 2017
Fibrotic
diseases
are
characterized
by
net
accumulation
of
extracellular
matrix
proteins
in
affected
organs
leading
to
their
dysfunction
and
ultimate
failure.
Myofibroblasts
have
been
identified
as
the
cells
responsible
for
progression
fibrotic
process,
they
originate
from
several
sources,
including
quiescent
tissue
fibroblasts,
circulating
CD34+
fibrocytes
phenotypic
conversion
various
cell
types
into
activated
myofibroblasts.
Several
studies
demonstrated
that
endothelial
can
transdifferentiate
mesenchymal
through
a
process
termed
endothelial-
transition
(EndMT)
this
give
rise
myofibroblasts
involved
development
diseases.
Transforming
growth
factor
β
(TGF-β)
has
central
role
fibrogenesis
modulating
fibroblast
phenotype
function,
inducing
myofibroblast
transdifferentiation
promoting
accumulation.
In
addition,
TGF-β
EndMT
may
further
contribute
fibrosis.
Despite
extensive
investigation
pathogenesis
diseases,
no
effective
treatment
strategies
available.
Delineation
mechanisms
initiation
is
crucial
therapeutic
disease.
review,
we
summarize
signaling
pathway
discuss
potential.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: June 9, 2022
Abstract
Chronic
kidney
disease
(CKD)
is
a
chronic
renal
dysfunction
syndrome
that
characterized
by
nephron
loss,
inflammation,
myofibroblasts
activation,
and
extracellular
matrix
(ECM)
deposition.
Lipotoxicity
oxidative
stress
are
the
driving
force
for
loss
of
including
tubules,
glomerulus,
endothelium.
NLRP3
inflammasome
signaling,
MAPK
PI3K/Akt
RAAS
signaling
involves
in
lipotoxicity.
The
upregulated
Nox
expression
decreased
Nrf2
result
directly.
injured
resident
cells
release
proinflammatory
cytokines
chemokines
to
recruit
immune
such
as
macrophages
from
bone
marrow.
NF-κB
JAK-STAT
Toll-like
receptor
cGAS-STING
major
pathways
mediate
inflammation
inflammatory
cells.
produce
secret
great
number
profibrotic
TGF-β1,
Wnt
ligands,
angiotensin
II.
TGF-β
Notch
evoke
activation
promote
generation
ECM.
potential
therapies
targeted
these
also
introduced
here.
In
this
review,
we
update
key
lipotoxicity,
stress,
kidneys
with
injury,
drugs
based
on
latest
studies.
Unifying
will
be
instrumental
advance
further
basic
clinical
investigation
CKD.
Journal of the American Society of Nephrology,
Journal Year:
2017,
Volume and Issue:
29(1), P. 182 - 193
Published: Oct. 11, 2017
The
Wnt/
β
-catenin
pathway
is
crucial
in
normal
development
and
throughout
life,
but
aberrant
activation
of
this
has
been
linked
to
kidney
fibrosis,
although
the
mechanisms
involved
remain
incompletely
determined.
Here,
we
investigated
role
regulating
macrophage
contribution
thereof
fibrosis.
Treatment
macrophages
with
Wnt3a
exacerbated
IL-4–
or
TGF
1-induced
alternative
(M2)
polarization
phosphorylation
nuclear
translocation
STAT3
vitro
.
Conversely,
inhibition
signaling
prevented
these
processes.
In
a
mouse
model,
induced
deletion
attenuated
accumulation,
M2
observed
kidneys
wild-type
littermates
after
unilateral
ureter
obstruction.
This
study
shows
that
promotes
fibrosis
by
stimulating
polarization.
