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Upregulation of serotonin-receptor-2a and serotonin transporter expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.
[congenital diaphragmatic hernia]
Congenital
diaphragmatic
hernia
(
CDH
)
is
attributed
to
severe
pulmonary
hypoplasia
and
pulmonary
hypertension
(
PH
)
.
PH
is
characterized
by
structural
changes
resulting
in
vascular
remodeling
.
Serotonin
,
a
potent
vasoconstrictor
,
plays
a
central
role
in
the
development
of
PH
.
It
exerts
its
constricting
effects
on
the
vessels
via
Serotonin
receptor
2
A
(
5
-
HT
2
A
)
and
induces
pulmonary
smooth
muscle
cell
proliferation
via
the
serotonin
transporter
(
5
-
HTT
)
.
This
study
was
designed
to
investigate
expressions
of
5
-
HT
2
A
and
5
-
HTT
in
the
pulmonary
vasculature
of
rats
with
nitrofen-induced
CDH
.
R
ats
were
exposed
to
nitrofen
or
vehicle
on
D
9
.
Fetuses
were
sacrificed
on
D
21
and
divided
into
nitrofen
and
control
group
(
n
=
32
)
.
Pulmonary
RNA
was
extracted
and
mRNA
level
of
5
HT
2
A
was
determined
by
qRT-PCR
.
Protein
expression
of
5
HT
2
A
and
5
-
HTT
was
investigated
by
western
blotting
.
Confocal
immunofluorescence
double
-staining
for
5
-
HT
2
A
,
5
-
HTT
,
and
alpha
smooth
muscle
actin
were
performed
.
Pulmonary
5
-
HT
2
A
gene
expression
levels
were
significantly
increased
in
nitrofen-induced
CDH
compared
to
controls
.
Western
blotting
and
confocal
microscopy
confirmed
increased
pulmonary
protein
expression
in
CDH
lungs
compared
to
controls
.
Increased
gene
and
protein
expression
of
5
HT
2
A
and
5
-
HTT
in
the
pulmonary
vasculature
of
nitrofen-induced
CDH
lungs
suggest
that
5
HT
2
A
and
5
-
HTT
are
important
mediators
of
PH
in
nitrofen-induced
CDH
.
