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Characterization of immortalized human epidermolysis bullosa simplex (KRT5) cell lines: trimethylamine N-oxide protects the keratin cytoskeleton against disruptive stress condition.
[epidermolysis bullosa simplex]
Epidermolysis
bullosa
simplex
(
EBS
)
is
an
autosomal
inherited
mechano-bullous
disease
,
characterized
by
intraepidermal
blistering
and
skin
fragility
caused
by
mutations
in
the
keratin
(
KRT
)
5
or
14
genes
.
Despite
a
vast
knowledge
about
the
intermediate
filament
pathology
in
this
disease
,
the
progress
in
therapy
has
been
slow
.
Animal
models
and
well-characterized
continuous
cell
culture
models
of
EBS
are
needed
prior
to
clinical
testing
.
Our
aim
was
to
generate
immortalized
cell
lines
as
an
in
vitro
model
for
the
study
of
EBS
and
test
a
chemical
chaperone
,
trimethylamine
N-
oxide
(
TMAO
)
,
as
a
putative
novel
therapy
.
We
generated
four
immortalized
cell
lines
,
two
each
from
an
EBS
patient
with
a
KRT
5
-
mutation
(
V
186
L
)
and
a
healthy
control
,
using
human
papillomavirus
16
(
HPV
16
)
E
6
E
7
as
transducer
.
Cell
lines
were
established
in
serum-free
and
serum-containing
medium
and
assessed
for
growth
characteristics
,
keratin
expression
profiles
,
ability
to
differentiate
in
organotypic
cultures
,
and
response
to
heat
stress
with
and
without
the
presence
of
TMAO
.
All
cell
lines
have
been
expanded
>
160
population
doublings
and
their
cellular
characteristics
are
similar
.
However
,
the
formation
of
cytoplasmic
keratin
filament
aggregates
in
response
to
heat-shock
treatment
differed
between
EBS
and
normal
cell
lines
.
Notably
,
serum-free
established
EBS
-cell
line
was
most
vulnerable
to
heat
shock
but
both
cell
lines
exhibited
significant
reduction
in
the
number
of
keratin
aggregates
containing
cells
by
TMAO
.
T
he
immortalized
cell
lines
represent
a
suitable
model
for
studying
novel
therapies
for
EBS
.
TMAO
is
a
promising
new
agent
for
future
development
as
a
novel
EBS
therapy
.
Diseases
Validation
Diseases presenting
"reduction in the number of keratin aggregates"
symptom
epidermolysis bullosa simplex
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