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Epimorphin expression in a rat model of pulmonary hypoplasia associated with congenital diaphragmatic hernia.
[congenital diaphragmatic hernia]
The
pathogenesis
of
pulmonary
hypoplasia
associated
with
congenital
diaphragmatic
hernia
(
CDH
)
remains
unclear
.
Interactions
between
the
epithelium
and
surrounding
mesenchyme
play
an
important
role
in
normal
lung
morphogenesis
.
Epimorphin
,
a
stromal
protein
,
plays
a
role
in
epithelial
morphogenesis
and
lung
branching
,
both
of
which
are
involved
in
pulmonary
hypoplasia
.
In
this
study
,
we
aimed
to
examine
the
relationship
between
epimorphin
and
pulmonary
hypoplasia
associated
with
CDH
in
an
animal
model
.
Time-pregnant
rats
were
exposed
to
nitrofen
or
vehicle
on
gestational
day
9
(
D
9
)
.
Fetuses
were
harvested
on
D
16
and
D
20
,
and
were
divided
into
control
,
hypoplastic
lungs
with
CDH
(
CDH
+
)
,
and
hypoplastic
lungs
without
CDH
(
CDH
-
)
.
Both
lungs
of
each
fetus
were
removed
and
subjected
to
morphometric
and
molecular
biologic
analyses
.
Lung
-
to
-body
weight
ratios
were
calculated
.
Pulmonary
RNA
was
extracted
,
and
relative
mRNA
level
of
epimorphin
was
determined
by
quantitative
real-time
PCR
(
qRT-PCR
)
.
Protein
expression
of
epimorphin
was
investigated
by
Western
blotting
.
In
groups
D
16
and
D
20
,
lung
-
to
-body
weight
ratios
in
subgroups
CDH
+
were
significantly
lower
than
those
of
controls
and
CDH
-
.
The
relative
mRNA
expression
levels
of
epimorphin
were
significantly
increased
in
both
lungs
in
subgroup
CDH
+
compared
with
controls
and
CDH
-
on
D
16
.
Pulmonary
epimorphin
gene
expression
levels
were
significantly
decreased
in
CDH
+
group
on
D
20
compared
to
controls
.
Western
blotting
confirmed
the
qRT-PCR
results
showing
decreased
pulmonary
epimorphin
protein
expression
in
CDH
+
hypoplastic
lungs
compared
to
controls
on
D
20
.
O
ur
study
shows
that
there
is
an
association
between
the
epimorphin
expression
and
pulmonary
hypoplasia
associated
with
CDH
.
Although
the
cause-effect
relationship
is
far
from
being
established
,
epimorphin-related
mechanisms
have
a
more
critical
role
in
early
(
D
16
)
developmental
stage
.
Diseases
Validation
Diseases presenting
"levels of epimorphin were significantly increased in both lungs in subgroup"
symptom
congenital diaphragmatic hernia
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