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Sphingosine-1-phosphate stimulated connective tissue growth factor expression in human buccal fibroblasts: Inhibition by epigallocatechin-3-gallate.
[oral submucous fibrosis]
Connective
tissue
growth
factor
(
CCN
2
)
has
been
associated
with
the
pathogenesis
of
various
fibrotic
diseases
,
including
oral
submucous
fibrosis
(
OSF
)
.
The
chemical
constituents
of
areca
nut
along
with
the
mechanical
trauma
cause
OSF
.
The
coarse
fibers
of
areca
nut
injure
the
mucosa
and
hence
sphingosine-
1
-
phosphate
(
S
1
P
)
is
released
at
the
wounded
sites
.
Recent
studies
have
shown
that
S
1
P
is
involved
in
wound
healing
and
the
development
of
fibrosis
.
The
aims
of
this
study
were
to
investigate
the
effects
of
S
1
P
on
CCN
2
expression
in
human
buccal
fibroblasts
(
HBFs
)
and
identify
the
potential
targets
for
drug
intervention
or
chemoprevention
of
OSF
.
W
estern
blot
analyses
were
used
to
study
the
effects
of
S
1
P
on
CCN
2
expression
and
its
signaling
pathways
in
HBFs
and
whether
epigallocatechin-
3
-
gallate
(
EGCG
)
,
the
main
and
most
significant
polyphenol
in
green
tea
,
could
inhibit
this
pathway
.
S
1
P
significantly
enhanced
CCN
2
synthesis
in
HBFs
.
This
effect
can
be
inhibited
by
c-
Jun
NH
2
-
terminal
kinase
(
JNK
)
inhibitor
and
extracellular
signal-regulated
kinase
inhibitor
but
not
by
P
38
mitogen-activated
protein
kinase
inhibitor
.
Interestingly
,
EGCG
completely
blocked
S
1
P
-
induced
CCN
2
expression
via
suppressing
S
1
P
-
induced
JNK
phosphorylation
.
S
1
P
released
by
repetitive
mechanical
trauma
during
AN
chewing
may
contribute
to
the
pathogenesis
of
OSF
through
upregulating
CCN
2
expression
in
HBFs
.
EGCG
could
be
an
adjuvant
to
the
current
offered
therapy
options
or
the
prevention
of
OSF
through
suppression
of
JNK
activation
.
Diseases
Validation
Diseases presenting
"growth factor"
symptom
22q11.2 deletion syndrome
achondroplasia
adrenal incidentaloma
aniridia
cadasil
cholangiocarcinoma
coats disease
dedifferentiated liposarcoma
dentin dysplasia
dentinogenesis imperfecta
dystrophic epidermolysis bullosa
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
holt-oram syndrome
inclusion body myositis
kallmann syndrome
krabbe disease
liposarcoma
lymphangioleiomyomatosis
oculocutaneous albinism
oral submucous fibrosis
pleomorphic liposarcoma
primary effusion lymphoma
primary hyperoxaluria type 1
severe combined immunodeficiency
systemic capillary leak syndrome
von hippel-lindau disease
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
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