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Hypoxic regulation of plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts stimulated with arecoline.
[oral submucous fibrosis]
Oral
submucous
fibrosis
(
OSF
)
is
regarded
as
a
pre-cancerous
condition
with
fibrosis
in
oral
subepithelial
connective
tissue
.
Hypoxia-inducible
factor
(
HIF
)
-
1
α
regulates
a
wide
variety
of
profibrogenic
genes
,
which
are
closely
associated
with
tissue
fibrosis
.
The
aim
of
this
study
was
to
compare
HIF-
1
α
expression
in
normal
buccal
mucosa
tissues
and
OSF
specimens
and
further
explore
the
potential
mechanisms
that
may
lead
to
the
induction
of
HIF-
1
α
expression
.
Twenty
-
five
OSF
specimens
and
six
normal
buccal
mucosa
were
examined
by
immunohistochemistry
.
The
expression
of
HIF-
1
α
from
fibroblasts
cultured
from
OSF
and
normal
buccal
mucosa
was
measured
by
Western
blot
.
Arecoline
,
a
major
areca
nut
alkaloid
,
was
challenged
to
normal
buccal
mucosa
fibroblasts
(
BMFs
)
to
elucidate
whether
HIF-
1
α
expression
could
affect
by
arecoline
.
In
addition
,
the
effects
of
arecoline
on
plasminogen
activator
inhibitor
(
PAI
)
-
1
expression
were
evaluated
in
environmental
hypoxia
.
H
IF-
1
α
expression
was
significantly
higher
in
OSF
specimens
and
expressed
mainly
by
fibroblasts
,
epithelial
cells
,
and
inflammatory
cells
.
Fibroblasts
derived
from
OSF
were
found
to
exhibit
higher
HIF-
1
α
protein
expression
than
BMFs
(
P
Â
<
Â
0
.
05
)
.
Arecoline
was
found
to
upregulate
HIF-
1
α
protein
in
a
dose-dependent
manner
(
P
Â
<
Â
0
.
05
)
.
Hypoxia
increased
arecoline-induced
PAI-
1
protein
expression
than
normoxic
conditions
(
P
Â
<
Â
0
.
05
)
.
These
results
suggest
that
HIF-
1
α
expression
is
significantly
upregulated
in
OSF
tissues
from
areca
quid
chewers
,
implying
a
potential
role
as
a
biomarker
for
local
tissue
hypoxia
.
The
activation
of
HIF-
1
α
may
promote
fibrogenesis
by
an
increase
of
PAI-
1
expression
and
a
subsequent
elevation
of
extracellular
matrix
production
in
oral
submucosa
leading
to
fibrosis
.
Diseases
Validation
Diseases presenting
"inflammatory cells"
symptom
allergic bronchopulmonary aspergillosis
alpha-thalassemia
focal myositis
hodgkin lymphoma, classical
inclusion body myositis
oral submucous fibrosis
wiskott-aldrich syndrome
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