Role of ALDH3A1 in Maintaining the Balance between Alveolar Type 1 and Type 2 Cells in Emphysema: From Patient to Organoid Model
Abstract
Background:
Chronic
obstructive
pulmonary
disease
(COPD)
is
characterized
by
alveolar
destruction,
which
called
emphysema.
Alveoli
are
mainly
composed
of
type
1
(AT1)
and
2
(AT2)
cells;
however,
the
specific
mechanisms
regulating
AT1
AT2
during
development
emphysema
remain
unclear.
Methods:
This
study
performed
single-cell
sequencing
(scSeq)
pseudo-time
analysis
on
primary
human
cells
exposed
to
cigarette
smoke
extract
(CSE).
Subsequently,
a
(CS)-induced
mouse
model
was
established
using
nasal-oral
exposure
system,
an
intervention
created
intraperitoneal
injection
dexamethasone
(DEX)
solution.
Pulmonary
function
tests,
H&E
staining,
immunochemistry,
immunofluorescence
staining
were
conducted
in
mice.
Additionally,
organoids,
in
vitro
models
CSE-induced
model,
DEX
ALDH3A1
overexpression
established,
followed
flow
cytometry,
RT-qPCR,
western
blot
assays.
Results:
Analysis
scSeq
data
showed
that
lung
CSE
exhibited
imbalance
ratio
cells,
with
decreased
expression
cells.
In
vivo
significantly
reduced,
structure
severely
damaged
increased
mean
linear
intercept.
The
aquaporin
5
(AQP5)+
surfactant
protein
C
(SFTPC)+
decreased,
accompanied
emphysema;
further,
treatment
protected
lungs
against
CS-induced
Using
organoid,
gene
levels
dose-dependent
manner
ratio.
could
not
rescue
completely.
More
critically,
effectively
protects
organoids
between
Conclusion:
confirms
crucial
role
maintaining
structure;
ALDH3A1-independent
manner.
importantly,
murine
organoid
successfully
resembles
alteration
lungs,
providing
useful
for
mechanism
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Дек. 30, 2024
Язык: Английский
