Expert Opinion on Investigational Drugs,
Год журнала:
2025,
Номер
unknown, С. 1 - 20
Опубликована: Фев. 7, 2025
Idiopathic
pulmonary
fibrosis
(IPF)
is
a
chronic,
progressive
fibrosing
interstitial
lung
disease
of
unknown
cause
that
occurs
primarily
in
older
adults
and
associated
with
poor
quality
life
substantial
healthcare
utilization.
IPF
has
dismal
prognosis.
Indeed,
first-line
therapy,
which
includes
nintedanib
pirfenidone,
does
not
stop
progression
often
tolerability
issues.
Therefore,
there
remains
high
medical
need
for
more
efficacious
better
tolerated
treatments.
Gene
therapy
relatively
unexplored
field
research
the
potential
to
mitigate
range
profibrotic
pathways
by
introducing
genetic
material
into
cells.
Here,
we
summarize
critically
discuss
publications
have
explored
safety
efficacy
gene
experimentally-induced
animals,
as
clinical
studies
humans
been
published
yet.
The
application
requires
further
investigation
address
several
technical
biological
hurdles,
improve
vectors'
design,
drug
delivery,
target
selection,
off-target
effects
develop
markers
penetration
Long-term
data
are
needed
bring
one
step
closer
practice.
Molecular Medicine,
Год журнала:
2023,
Номер
29(1)
Опубликована: Апрель 25, 2023
Abstract
Background
Myofibroblasts
(MFB),
one
of
the
major
effectors
pathologic
fibrosis,
mainly
derived
from
activation
fibroblast
to
myofibroblast
transition
(FMT).
Although
MFBs
were
historically
considered
terminally
differentiated
cells,
their
potential
for
de-differentiation
was
recently
recognized
and
implied
with
therapeutic
value
in
treating
fibrotic
diseases,
instance,
idiopathic
pulmonary
fibrosis
(IPF)
post
allogeneic
hematopoietic
stem
cell
transplantation
bronchiolitis
obliterans
(BO).
During
past
decade,
several
methods
reported
block
or
reverse
MFB
differentiation,
among
which
mesenchymal
cells
(MSC)
have
demonstrated
but
undetermined
values.
However,
MSC-mediated
regulation
FMT
underlying
mechanisms
remained
largely
undefined.
Method
By
identifying
TGF-β1
hypertension
as
pivotal
landmark
during
pro-fibrotic
FMT,
TGF-β1-induced
MSC
co-culture
models
established
utilized
investigate
regulations
by
on
vitro.
Methods
including
RNA
sequencing
(RNA-seq),
Western
blot,
qPCR
flow
cytometry
used.
Result
Our
data
revealed
that
readily
induced
invasive
signatures
identified
tissues
initiated
differentiation
normal
FB.
reversibly
de-differentiated
into
a
group
FB-like
selectively
inhibiting
TGF-β-SMAD2/3
signaling.
Importantly,
these
proliferation-boosted
sensitive
could
be
re-induced
MFB.
Conclusion
findings
highlighted
reversibility
through
signaling,
may
explain
MSC's
inconsistent
clinical
efficacies
BO
other
diseases.
These
are
still
further
deteriorate
phenotypes
unless
microenvironment
is
corrected.
Journal of Molecular Medicine,
Год журнала:
2023,
Номер
101(10), С. 1169 - 1189
Опубликована: Авг. 22, 2023
Abstract
Tissue-resident
fibroblasts
are
mesenchymal
cells
which
control
the
structural
integrity
of
extracellular
matrix
(ECM).
Fibroblasts
possess
a
remarkable
plasticity
to
allow
them
adapt
changes
in
microenvironment
and
thus
maintain
tissue
homeostasis.
Several
stresses,
also
those
associated
with
aging
process,
convert
quiescent
into
myofibroblasts
not
only
display
fibrogenic
properties
but
act
as
immune
regulators
cooperating
both
tissue-resident
recruited
affected
tissues.
TGF-β
cytokine
reactive
oxygen
species
(ROS)
major
inducers
myofibroblast
differentiation
pathological
conditions
either
from
or
via
transdifferentiation
certain
other
cell
types,
e.g.,
macrophages,
adipocytes,
pericytes,
endothelial
cells.
Intriguingly,
ROS
important
signaling
mediators
between
immunosuppressive
cells,
such
MDSCs,
Tregs,
M2
macrophages.
It
seems
that
states,
able
interact
network.
There
is
clear
evidence
low-grade
chronic
inflammatory
state
tissues
counteracted
by
activation
compensatory
immunosuppression.
Interestingly,
common
enhancers
oxidative
stress,
loss
DNA
integrity,
insults,
myofibroblasts,
whereas
anti-aging
treatments
metformin
rapamycin
suppress
prevent
age-related
fibrosis.
I
will
examine
reciprocal
interactions
within
harmful
stresses
enhances
activity
network
promotes
fibrosis
degeneration
elderly
individuals.
Journal of Cellular and Molecular Medicine,
Год журнала:
2022,
Номер
26(20), С. 5113 - 5121
Опубликована: Сен. 15, 2022
Abstract
Disturbances
or
defects
in
the
process
of
wound
repair
can
disrupt
delicate
balance
cells
and
molecules
necessary
for
complete
healing,
thus
leading
to
chronic
wounds
fibrotic
scars.
Myofibroblasts
are
one
most
important
involved
scars,
reprogramming
provides
a
potential
avenue
increase
myofibroblast
clearance.
Although
myofibroblasts
have
long
been
recognized
as
terminally
differentiated
cells,
recent
studies
shown
that
capacity
be
reprogrammed
into
adipocytes.
This
review
intends
summarize
We
will
discuss
lineage
tracing,
well
known
mechanisms
underlying
adipocyte
regeneration
from
myofibroblasts.
In
addition,
we
investigated
different
changes
gene
expression,
transcriptional
regulators,
signalling
pathways
epigenetic
regulators
during
skin
healing.
future,
healing
better
understood
appreciated,
which
may
provide
new
ideas
treatment
scarless
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Фев. 14, 2023
Idiopathic
pulmonary
fibrosis
(IPF)
is
a
chronic,
progressive
interstitial
lung
disease
(ILD)
without
an
identifiable
cause.
If
not
treated
after
diagnosis,
the
average
life
expectancy
3–5
years.
Currently
approved
drugs
for
treatment
of
IPF
are
Pirfenidone
and
Nintedanib,
as
antifibrotic
drugs,
which
can
reduce
decline
rate
forced
vital
capacity
(FVC)
risk
acute
exacerbation
IPF.
However
these
relieve
symptoms
associated
with
IPF,
nor
improve
overall
survival
patients.
We
need
to
develop
new,
safe
effective
treat
fibrosis.
Previous
studies
have
shown
that
cyclic
nucleotides
participate
in
pathway
play
essential
role
process
Phosphodiesterase
(PDEs)
involved
nucleotide
metabolism,
so
PDE
inhibitors
candidates
This
paper
reviews
research
progress
related
fibrosis,
provide
ideas
development
anti-pulmonary
drugs.
Expert Opinion on Investigational Drugs,
Год журнала:
2025,
Номер
unknown, С. 1 - 20
Опубликована: Фев. 7, 2025
Idiopathic
pulmonary
fibrosis
(IPF)
is
a
chronic,
progressive
fibrosing
interstitial
lung
disease
of
unknown
cause
that
occurs
primarily
in
older
adults
and
associated
with
poor
quality
life
substantial
healthcare
utilization.
IPF
has
dismal
prognosis.
Indeed,
first-line
therapy,
which
includes
nintedanib
pirfenidone,
does
not
stop
progression
often
tolerability
issues.
Therefore,
there
remains
high
medical
need
for
more
efficacious
better
tolerated
treatments.
Gene
therapy
relatively
unexplored
field
research
the
potential
to
mitigate
range
profibrotic
pathways
by
introducing
genetic
material
into
cells.
Here,
we
summarize
critically
discuss
publications
have
explored
safety
efficacy
gene
experimentally-induced
animals,
as
clinical
studies
humans
been
published
yet.
The
application
requires
further
investigation
address
several
technical
biological
hurdles,
improve
vectors'
design,
drug
delivery,
target
selection,
off-target
effects
develop
markers
penetration
Long-term
data
are
needed
bring
one
step
closer
practice.
