bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: July 26, 2023
Abstract
Aging
is
the
main
risk
factor
for
chronic
lung
diseases
including
idiopathic
pulmonary
fibrosis
(IPF)
and
obstructive
disease
(COPD).
Accordingly,
hallmarks
of
aging
such
as
cellular
senescence
are
increased
in
different
cell
types
fibroblasts
lungs
these
patients.
However,
whether
senescent
phenotype
derived
from
IPF
or
COPD
differs
still
unknown.
Therefore,
we
characterized
at
baseline
after
exposure
to
disease-relevant
insults
(H
2
O
,
bleomycin,
TGF-β1)
cultured
primary
human
(phLF)
control
donors,
IPF,
We
found
that
phLF
disease-origins
have
a
low
senescence.
H
bleomycin
treatment
induced
whereas
TGF-β1
only
had
pro-fibrotic
effect.
Interestingly,
did
not
observe
any
differences
susceptibility
induction
based
on
origin.
stimuli
resulted
programs
phLF.
Moreover,
reduced
colony
formation
efficiency
alveolar
epithelial
progenitor
cells.
In
conclusion,
mainly
determined
by
inducer
impairs
capacity
vitro
.
Biochemical Journal,
Journal Year:
2023,
Volume and Issue:
480(23), P. 1987 - 2008
Published: Dec. 6, 2023
Interleukin
11
(IL11)
is
an
elusive
member
of
the
IL6
family
cytokines.
While
initially
thought
to
be
a
haematopoietic
and
cytoprotective
factor,
more
recent
data
show
instead
that
IL11
redundant
for
haematopoiesis
toxic.
In
this
review,
reasons
led
original
misunderstandings
biology,
which
are
now
understandable,
explained
with
particular
attention
on
use
recombinant
human
in
mice
humans.
Following
tissue
injury,
as
part
evolutionary
ancient
homeostatic
response,
secreted
from
damaged
mammalian
cells
signal
via
JAK/STAT3,
ERK/P90RSK,
LKB1/mTOR
GSK3β/SNAI1
autocrine
paracrine.
This
activates
program
mesenchymal
transition
epithelial,
stromal,
endothelial
cause
inflammation,
fibrosis,
stalled
endogenous
repair,
leading
organ
failure.
The
role
signalling
cell-
organ-specific
pathobiology
described,
large
unknowns
about
biology
discussed
promise
targeting
therapeutic
approach
reviewed.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: May 17, 2023
Interstitial
lung
disease
(ILD)
is
a
heterogenous
group
of
disorders
where
destruction
and
incomplete
regeneration
the
parenchyma
often
results
in
persistent
architectural
distortion
pulmonary
scaffold.
Continuous
mesenchyme-centered,
disease-relevant
signaling
likely
initiates
perpetuates
fibrotic
remodeling
process,
specifically
targeting
epithelial
cell
compartment,
thereby
destroying
gas
exchange
area.
Clinical & Experimental Immunology,
Journal Year:
2023,
Volume and Issue:
214(2), P. 154 - 161
Published: Sept. 19, 2023
Interleukin-11
is
a
cytokine
from
the
IL-6
family
of
cytokines
that
includes
and
oncostatin-M.
Initially
described
for
its
role
in
platelet
generation,
it
now
appreciated
this
has
multiple
functions.
Recently
been
found
IL-11
critical
fibrosis
different
organ
systems
systemically
as
autoimmune
disease
systemic
sclerosis.
Animal
models
have
determined
animals
with
receptor
deletions
retarded
wild-type
at
fibrosis.
Recent
evidence
suggests
may
be
master
regulator
regardless
end
target
organ.
With
development
neutralizing
antibodies
targeting
pre-clinical
could
possible
therapeutic,
which
no
specific
therapies
exist.
This
review
appraises
tissue
fibrosis,
signalling
properties,
therapeutic
targeting.
The
ends
an
appraisal
indications
modulation
targeted.
npj Regenerative Medicine,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: March 25, 2025
There
is
an
urgent
need
for
innovative
therapies
targeting
defective
epithelial
repair
in
chronic
diseases
like
COPD.
The
mesenchymal
niche
a
critical
regulator
stem
cell
activation,
suggesting
that
their
secreted
factors
are
possible
potent
drug
targets.
Utilizing
proteomics-guided
discovery
strategy,
we
explored
the
lung
fibroblast
secretome
to
uncover
impactful
Our
organoid
assays
identified
several
regenerative
ligands,
with
osteoglycin
(OGN)
showing
most
profound
effects.
Transcriptomic
analyses
revealed
OGN
enhances
alveolar
progenitor
differentiation,
detoxifies
reactive
oxygen
species,
and
strengthens
fibroblast-epithelial
crosstalk.
expression
was
diminished
COPD
patients
smoke-exposed
mice.
An
active
fragment
of
(leucine-rich
repeat
regions
4-7)
replicated
full-length
OGN's
effects,
significantly
ameliorating
elastase-induced
injury
slices
improving
function
vivo.
These
findings
highlight
as
pivotal
protein
repair,
positioning
its
promising
therapeutic
Cells,
Journal Year:
2024,
Volume and Issue:
13(13), P. 1129 - 1129
Published: June 29, 2024
Aging
is
the
main
risk
factor
for
chronic
lung
diseases
(CLDs)
including
idiopathic
pulmonary
fibrosis
(IPF)
and
obstructive
disease
(COPD).
Accordingly,
hallmarks
of
aging
like
cellular
senescence
are
increased
in
these
patients
different
cell
types
fibroblasts.
However,
little
known
about
triggers
that
induce
a
phenotype
backgrounds
its
role
CLD
pathogenesis.
Therefore,
we
characterized
primary
human
fibroblasts
(phLF)
from
control,
IPF,
or
COPD
at
baseline
after
exposure
to
disease-relevant
insults
(H2O2,
bleomycin,
TGF-β1)
studied
their
capacity
support
progenitor
potential
organoid
model.
Bulk-RNA
sequencing
revealed
phLF
IPF
activate
transcriptional
programs
but
share
similar
baseline.
Moreover,
H2O2
bleomycin
not
TGF-β1
induced
origins.
Exposure
resulted
distinct
by
SASP
profiles.
Finally,
co-culture
with
bleomycin-
H2O2-treated
reduced
alveolar
epithelial
cells.
In
conclusion,
conserved
response
varies
depending
on
insult
impairs
ex
vivo.
Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
30(1)
Published: Nov. 23, 2024
Abstract
Impaired
interaction
of
fibroblasts
with
pneumocytes
contributes
to
the
progression
chronic
lung
disease
such
as
idiopathic
pulmonary
fibrosis
(IPF).
Mucin
5B
(MUC5B)
is
associated
IPF.
Here
we
analyzed
primary
and
alveolar
type
2
(AT2)
in
organoid
model.
Single-cell
analysis,
histology,
qRT-PCR
revealed
that
expressing
high
levels
markers
regulate
STAT3
signaling
AT2
cells,
which
accompanied
by
cystic
growth
MUC5B
expression.
Cystic
expression
were
also
caused
cytokine
IL-6.
The
PI3K-Akt
pathway
was
activated
fibroblasts.
drug
dasatinib
prevented
formation
MUC5B-expressing
organoids.
cells
samples
obtained
from
IPF
patients.
Our
model
shows
fibrotic
induce
impaired
differentiation
via
pathways,
observed
It
can
be
used
for
mechanistic
studies
development.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 29, 2024
Abstract
Aging
is
the
main
risk
factor
for
chronic
lung
diseases
(CLDs)
including
idiopathic
pulmonary
fibrosis
(IPF)
and
obstructive
disease
(COPD).
Accordingly,
hallmarks
of
aging
such
as
cellular
senescence
are
present
in
different
cell
types
fibroblasts
these
patients.
However,
whether
senescent
phenotype
derived
from
IPF
or
COPD
patients
differs
still
unknown.
Therefore,
we
characterized
at
baseline
after
exposure
to
disease-relevant
insults
(H
2
O
,
bleomycin,
TGF-β1)
cultured
primary
human
(phLF)
control
donors,
IPF,
We
found
that
phLF
disease-origins
have
a
low
senescence.
H
bleomycin
treatment
induced
phLF,
whereas
TGF-β1
had
primarily
pro-fibrotic
effect.
Notably,
did
not
observe
any
differences
susceptibility
induction
based
on
origin,
while
stimuli
resulted
distinct
programs
phLF.
Moreover,
reduced
colony
formation
efficiency
distal
alveolar
epithelial
progenitor
cells
stimuli-dependent
manner.
In
conclusion,
mainly
determined
by
inducer
impairs
capacity
vitro
.
