Proceedings of the National Academy of Sciences,
Journal Year:
2019,
Volume and Issue:
116(26), P. 12980 - 12985
Published: June 11, 2019
Significance
Increased
hydrostatic
pressure
in
lung
capillaries
experienced
during
high
altitude,
head
trauma,
and
left
heart
failure
can
lead
to
disruption
of
endothelial
barrier
edema
formation.
We
identified
Piezo1
as
a
mechanical
sensor
responsible
for
breakdown
(barotrauma)
secondary
reduced
expression
the
adherens
junction
proteins
VE-cadherin,
β-catenin,
p120-catenin.
Endothelial-specific
deletion
or
pharmacological
inhibition
prevented
capillary
leakage,
suggesting
therapeutic
approach
preventing
associated
failure.
Journal of Clinical Investigation,
Journal Year:
2016,
Volume and Issue:
126(12), P. 4527 - 4536
Published: Oct. 30, 2016
Arterial
blood
pressure
is
controlled
by
vasodilatory
factors
such
as
nitric
oxide
(NO)
that
are
released
from
the
endothelium
under
influence
of
fluid
shear
stress
exerted
flowing
blood.
Flow-induced
endothelial
release
ATP
and
subsequent
activation
Gq/G11-coupled
purinergic
P2Y2
receptors
have
been
shown
to
mediate
stress-induced
stimulation
NO
formation.
However,
mechanism
which
initiates
these
processes
unclear.
Here,
we
mechanosensitive
cation
channel
PIEZO1
required
for
flow-induced
P2Y2/Gq/G11-mediated
downstream
signaling
results
in
phosphorylation
AKT
NOS.
We
also
demonstrated
PIEZO1-dependent
mediated
part
pannexin
channels.
The
activator
Yoda1
mimicked
effect
on
cells
induced
vasorelaxation
a
manner.
Furthermore,
mice
with
endothelium-specific
deficiency
lost
ability
induce
formation
vasodilation
response
flow
consequently
developed
hypertension.
Together,
our
data
demonstrate
regulation
formation,
vascular
tone,
pressure.
Nature Communications,
Journal Year:
2016,
Volume and Issue:
7(1)
Published: Jan. 20, 2016
Abstract
Mechanosensitive
ion
channels
are
force-transducing
enzymes
that
couple
mechanical
stimuli
to
flux.
Understanding
the
gating
mechanism
of
mechanosensitive
is
challenging
because
stimulus
seen
by
channel
reflects
forces
shared
between
membrane,
cytoskeleton
and
extracellular
matrix.
Here
we
examine
whether
PIEZO1
activated
force-transmission
through
bilayer.
To
achieve
this,
generate
HEK293
cell
membrane
blebs
largely
free
cytoskeleton.
Using
bacterial
MscL,
calibrate
bilayer
tension
demonstrating
activation
MscL
in
identical
reconstituted
bilayers.
Utilizing
a
novel
PIEZO1–GFP
fusion,
then
show
bleb
membranes,
at
lower
pressures
indicative
removal
cortical
mechanoprotection
it
provides.
Thus,
must
sense
force
directly
transmitted
