Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(22)
Опубликована: Сен. 28, 2023
Idiopathic
Pulmonary
Fibrosis
(IPF)
is
a
progressive
scarring
disease
arising
from
impaired
regeneration
of
the
alveolar
epithelium
after
injury.
During
regeneration,
type
2
epithelial
cells
(AEC2s)
assume
transitional
state
that
upregulates
multiple
keratins,
and
ultimately
differentiate
into
AEC1s.
In
IPF,
AECs
accumulate
with
ineffectual
AEC1
differentiation.
However,
whether
how
cause
fibrosis,
keratins
regulate
cell
accumulation
why
fibrosis
resolve
in
mouse
models
but
IPF
are
unclear.
Here,
we
show
human
keratin
(KRT)
8
genetic
variants
associated
IPF.
Krt8-/-
mice
protected
state.
Keratin
(K)
regulates
expression
macrophage
chemokines
recruitment.
Profibrotic
macrophages
myofibroblasts
promote
AECs,
establishing
K8-dependent
positive
feedback
loop
driving
fibrogenesis.
Finally,
rare
murine
highly
senescent,
basaloid,
do
not
AEC1s,
recapitulating
aberrant
basaloid
We
conclude
induce
maintained
by
manner;
mice,
most
resolve,
whereas
evolve
an
which
persists
fibrosis.
Annual Review of Pathology Mechanisms of Disease,
Год журнала:
2021,
Номер
17(1), С. 515 - 546
Опубликована: Ноя. 23, 2021
The
pathogenesis
of
idiopathic
pulmonary
fibrosis
(IPF)
involves
a
complex
interplay
cell
types
and
signaling
pathways.
Recurrent
alveolar
epithelial
(AEC)
injury
may
occur
in
the
context
predisposing
factors
(e.g.,
genetic,
environmental,
epigenetic,
immunologic,
gerontologic),
leading
to
metabolic
dysfunction,
senescence,
aberrant
activation,
dysregulated
repair.
interacts
with
mesenchymal,
immune,
endothelial
cells
via
multiple
mechanisms
trigger
fibroblast
myofibroblast
activation.
Recent
single-cell
RNA
sequencing
studies
IPF
lungs
support
model.
These
have
uncovered
novel
type
AEC
characteristics
an
basal
cell,
which
disrupt
normal
repair
propagate
profibrotic
phenotype.
Here,
we
review
bioinformatics
tools
as
strategies
discover
pathways
disease,
cell-specific
mechanisms,
cell-cell
interactions
that
niche.
Cells,
Год журнала:
2021,
Номер
10(2), С. 436 - 436
Опубликована: Фев. 18, 2021
Fibrosis
progression
in
the
lung
commonly
results
impaired
functional
gas
exchange,
respiratory
failure,
or
even
death.
In
addition
to
aberrant
activation
and
differentiation
of
fibroblasts,
persistent
alveolar
injury
incomplete
repair
are
driving
factors
fibrotic
response.
Macrophages
activated
polarized
response
lipopolysaccharide-
bleomycin-induced
injury.
The
classically
macrophage
(M1)
alternatively
(M2)
have
been
extensively
investigated
injury,
repair,
fibrosis.
present
review,
we
summarized
current
data
on
monocyte-derived
macrophages
that
recruited
lung,
as
well
resident
their
polarization,
pyroptosis,
phagocytosis
acute
(ALI).
Additionally,
described
how
interact
with
epithelial
cells
during
repair.
Finally,
emphasized
role
polarization
pulmonary
response,
elucidated
potential
benefits
targeting
alleviating
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(5), С. 2566 - 2566
Опубликована: Март 4, 2021
Alveolar
type
II
(ATII)
cells
are
a
key
structure
of
the
distal
lung
epithelium,
where
they
exert
their
innate
immune
response
and
serve
as
progenitors
alveolar
I
(ATI)
cells,
contributing
to
epithelial
repair
regeneration.
In
healthy
lung,
ATII
coordinate
host
defense
mechanisms,
not
only
generating
restrictive
barrier,
but
also
orchestrating
mechanisms
secreting
surfactant
proteins,
which
important
in
protection
against
pathogen
exposure.
Moreover,
proteins
help
maintain
homeostasis
reduce
surface
tension
at
pulmonary
air–liquid
interface,
thereby
preventing
atelectasis
reducing
work
breathing.
may
contribute
fibroproliferative
reaction
by
growth
factors
proinflammatory
molecules
after
damage.
Indeed,
various
acute
chronic
diseases
associated
with
intensive
inflammation.
These
include
oedema,
respiratory
distress
syndrome,
fibrosis
numerous
interstitial
diseases,
characterized
hyperplastic
considered
an
essential
part
epithelialization
process
and,
consequently,
wound
healing.
The
aim
this
review
is
that
revising
physiologic
pathologic
role
play
as,
despite
what
has
been
learnt
last
few
decades
research,
origin,
phenotypic
regulation
crosstalk
these
still
remain,
part,
mystery.
