Rare Diseases Symptoms Automatic Extraction
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Nrf2 links epidermal barrier function with antioxidant defense.
[lamellar ichthyosis]
The
skin
provides
an
efficient
permeability
barrier
and
protects
from
microbial
invasion
and
oxidative
stress
.
Here
,
we
show
that
these
essential
functions
are
linked
through
the
Nrf
2
transcription
factor
.
To
test
the
hypothesis
that
activation
of
Nrf
2
provides
skin
protection
under
stress
conditions
,
we
determined
the
consequences
of
pharmacological
or
genetic
activation
of
Nrf
2
in
keratinocytes
.
Surprisingly
,
mice
with
enhanced
Nrf
2
activity
in
keratinocytes
developed
epidermal
thickening
,
hyperkeratosis
and
inflammation
resembling
lamellar
ichthyosis
.
This
resulted
from
upregulation
of
the
cornified
envelope
proteins
small
proline-rich
proteins
(
Sprr
)
2
d
and
2
h
and
of
secretory
leukocyte
peptidase
inhibitor
(
Slpi
)
,
which
we
identified
as
novel
Nrf
2
targets
in
keratinocytes
.
Since
Sprrs
are
potent
scavengers
of
reactive
oxygen
species
and
since
Slpi
has
antimicrobial
activities
,
their
upregulation
contributes
to
Nrf
2
's
protective
function
.
However
,
it
also
caused
corneocyte
fragility
and
impaired
desquamation
,
followed
by
alterations
in
the
epidermal
lipid
barrier
,
inflammation
and
overexpression
of
mitogens
that
induced
keratinocyte
hyperproliferation
.
These
results
identify
an
unexpected
role
of
Nrf
2
in
epidermal
barrier
function
,
which
needs
to
be
considered
for
pharmacological
use
of
Nrf
2
activators
.
Diseases
Validation
Diseases presenting
"epidermal thickening"
symptom
lamellar ichthyosis
This symptom has already been validated