BMC Nephrology,
Journal Year:
2020,
Volume and Issue:
21(1)
Published: July 13, 2020
Abstract
Chronic
kidney
disease
(CKD)
is
characterized
by
inflammation,
injury
and
fibrosis.
Dysregulated
innate
immune
responses
mediated
macrophages
play
critical
roles
in
progressive
renal
injury.
The
differentiation
polarization
of
into
pro-inflammatory
‘M1’
anti-inflammatory
‘M2’
states
represent
the
two
extreme
maturation
programs
during
tissue
However,
effects
macrophage
on
pathogenesis
CKD
are
not
fully
understood.
In
this
review,
we
discuss
mechanisms
underlying
role
initiation,
progression,
resolution
recurrence
CKD.
Macrophage
activation
initiated
through
recognition
conserved
endogenous
exogenous
molecular
motifs
pattern
receptors,
chiefly,
Toll-like
receptors
(TLRs),
which
located
cell
surface
endosomes,
NLR
inflammasomes,
positioned
cytosol.
Recent
data
suggest
that
genetic
variants
molecule
apolipoprotein
L1
(APOL1)
associated
with
increased
prevalence
people
African
descent,
mediate
an
atypical
M1
polarization.
Manipulation
may
offer
novel
strategies
to
address
dysregulated
immunometabolism
provide
a
complementary
approach
along
current
podocentric
treatment
for
glomerular
diseases.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 25, 2024
Abstract
Chronic
kidney
disease
(CKD)
is
a
public
health
problem
driven
by
myofibroblast
accumulation,
leading
to
interstitial
fibrosis.
Heterogeneity
recently
recognized
characteristic
in
fibroblasts
CKD,
but
the
role
of
different
populations
still
unclear.
Here,
we
characterize
proinflammatory
fibroblast
population
(named
CXCL-iFibro),
which
corresponds
an
early
state
differentiation
CKD.
We
demonstrate
that
CXCL-iFibro
co-localize
with
macrophages
and
participate
their
attraction,
switch
into
FOLR2+
from
CKD
stages
on.
In
vitro,
promote
ECM-secreting
myofibroblasts
through
WNT/β-catenin-dependent
pathway,
thereby
suggesting
reciprocal
crosstalk
between
these
macrophages.
Finally,
detection
at
predictive
poor
patient
prognosis,
shows
player
progression
demonstrates
clinical
relevance
our
findings.
Journal of Biological Chemistry,
Journal Year:
2018,
Volume and Issue:
293(50), P. 19290 - 19302
Published: Oct. 17, 2018
M2
macrophage
polarization
is
known
to
underlie
kidney
fibrosis.
We
previously
reported
that
most
of
the
members
Wnt
family
signaling
proteins
are
induced
in
fibrotic
kidneys.
Dysregulation
protein
Wnt5a
associated
with
fibrosis,
but
little
about
role
regulating
activation
results
Here,
using
murine
Raw
264.7
cells
and
bone
marrow-derived
macrophages,
we
found
enhanced
transforming
growth
factor
β1
(TGFβ1)-induced
as
well
expression
transcriptional
regulators
Yes-associated
(Yap)/transcriptional
coactivator
PDZ-binding
motif
(Taz).
Verteporfin
blockade
Yap/Taz
inhibited
both
Wnt5a-
TGFβ1-induced
polarization.
In
mouse
models
shRNA-mediated
knockdown
diminished
expression,
Moreover,
genetic
ablation
Taz
macrophages
attenuated
fibrosis
mice.
Collectively,
these
indicate
promotes
by
stimulating
Yap/Taz-mediated
Cancer Research,
Journal Year:
2019,
Volume and Issue:
79(16), P. 4160 - 4172
Published: July 2, 2019
Abstract
Tumor-associated
macrophages
(TAM)
play
pivotal
roles
in
tumor
progression
and
metastasis,
but
the
contribution
regulation
of
different
macrophage
populations
remain
unclear.
Here
we
show
that
Notch
signaling
plays
distinct
regulating
TAM
subsets
hepatocellular
carcinoma
(HCC).
Myeloid-specific
NOTCH
blockade
by
conditional
disruption
recombination
signal
binding
protein
Jκ
(RBPj
cKO)
significantly
delayed
growth
subcutaneously
inoculated
Lewis
lung
(LLC),
accelerated
orthotopically
hepatic
Hepa1-6
tumors
mice.
In
contrast
to
subcutaneous
LLC,
RBPj
cKO
increased
number
TAMs
despite
impeded
differentiation
monocyte-derived
(moTAM).
The
dominating
orthotopic
HCC
manifested
properties
Kupffer
cells
(KC)
hence
are
tentatively
named
KC-like
(kclTAM).
proliferation
kclTAMs
was
maintained
even
Ccr2−/−
mice,
which
moTAMs
were
genetically
blocked.
via
enhanced
β-catenin–dependent
WNT
signaling,
also
downregulated
IL12
upregulated
IL10
expression
likely
through
c-MYC.
addition,
myeloid-specific
facilitated
metastasis
colorectal
cancer
suppressed
suggesting
phenotype
promoting
liver-specific.
patient-derived
biopsies,
negatively
correlated
with
activation
CD68+
macrophages,
positively
advanced
stages.
Therefore,
impedes
moTAMs,
upregulates
Wnt/β-catenin
promote
protumor
cytokine
production
kclTAMs,
facilitating
cancer.
Significance:
These
findings
highlight
role
carcinoma.
BMC Nephrology,
Journal Year:
2020,
Volume and Issue:
21(1)
Published: July 13, 2020
Abstract
Chronic
kidney
disease
(CKD)
is
characterized
by
inflammation,
injury
and
fibrosis.
Dysregulated
innate
immune
responses
mediated
macrophages
play
critical
roles
in
progressive
renal
injury.
The
differentiation
polarization
of
into
pro-inflammatory
‘M1’
anti-inflammatory
‘M2’
states
represent
the
two
extreme
maturation
programs
during
tissue
However,
effects
macrophage
on
pathogenesis
CKD
are
not
fully
understood.
In
this
review,
we
discuss
mechanisms
underlying
role
initiation,
progression,
resolution
recurrence
CKD.
Macrophage
activation
initiated
through
recognition
conserved
endogenous
exogenous
molecular
motifs
pattern
receptors,
chiefly,
Toll-like
receptors
(TLRs),
which
located
cell
surface
endosomes,
NLR
inflammasomes,
positioned
cytosol.
Recent
data
suggest
that
genetic
variants
molecule
apolipoprotein
L1
(APOL1)
associated
with
increased
prevalence
people
African
descent,
mediate
an
atypical
M1
polarization.
Manipulation
may
offer
novel
strategies
to
address
dysregulated
immunometabolism
provide
a
complementary
approach
along
current
podocentric
treatment
for
glomerular
diseases.
