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Plasminogen activator inhibitor-2 is expressed in different types of congenital ichthyosis: in vivo evidence for its cross-linking into the cornified cell envelope by transglutaminase-1.
[harlequin ichthyosis]
Plasminogen
activator
inhibitor-
2
(
PAI-
2
)
,
a
regulatory
serpin
of
the
plasminogen
activator
(
PA
)
system
,
has
been
described
as
a
potential
component
of
the
cornified
cell
envelope
(
CE
)
.
Protease
inhibitors
are
essential
for
skin
homeostasis
and
in
particular
for
the
regulation
of
the
desquamation
process
.
Therefore
,
an
aberrant
expression
of
PAI-
2
could
be
involved
in
the
pathogenesis
of
certain
cornification
disorders
.
Evaluation
of
the
expression
of
PAI-
2
in
different
types
of
congenital
ichthyosis
,
especially
in
lamellar
ichthyosis
/
nonbullous
congenital
ichthyosiform
erythroderma
(
LI
/
NCIE
)
and
in
Netherton
syndrome
(
NTS
)
.
Demonstration
of
the
functional
relationship
between
PAI-
2
and
transglutaminase
(
TGase
)
-
1
.
U
sing
immunohistochemistry
we
evaluated
cryosections
from
individuals
suffering
from
LI
/
NCIE
(
n
=
67
)
,
NTS
(
n
=
6
)
,
ichthyosis
-follicularis-atrichia-
photophobia
syndrome
(
n
=
2
)
and
Harlequin
ichthyosis
(
n
=
1
)
in
comparison
with
psoriasis
vulgaris
and
healthy
skin
.
Moreover
,
we
assessed
the
respective
TGase-
1
activity
and
the
presence
of
TGase-
1
protein
.
A
functional
assay
was
developed
to
elucidate
whether
PAI-
2
is
a
substrate
for
TGase-
1
.
PAI-
2
is
expressed
in
different
types
of
congenital
ichthyosis
and
there
is
a
strong
correlation
between
TGase-
1
activity
and
PAI-
2
protein
signal
.
Double
staining
revealed
a
strong
colocalization
of
TGase-
1
activity
and
PAI-
2
protein
.
The
epidermal
incorporation
of
the
specific
PAI-
2
peptide
containing
a
TGase
binding
site
revealed
a
strong
pericellular
staining
in
the
stratum
granulosum
in
healthy
skin
.
In
contrast
,
TGase-
1
-
deficient
skin
showed
only
a
lamellar
staining
in
the
stratum
corneum
.
We
provide
in
vivo
evidence
that
PAI-
2
is
a
substrate
of
TGase-
1
.
The
normal
expression
of
PAI-
2
in
a
large
group
of
TGase-
1
-
proficient
LI
/
NCIE
patients
makes
it
rather
unlikely
that
PAI-
2
alone
is
a
primary
molecular
cause
of
LI
/
NCIE
.
Diseases
Validation
Diseases presenting
"ichthyosis"
symptom
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
harlequin ichthyosis
hirschsprung disease
junctional epidermolysis bullosa
kallmann syndrome
lamellar ichthyosis
This symptom has already been validated