| Abstract |
Duchenne muscular dystrophy (DMD) is the most frequent muscular dystrophy
in children. It is characterized by progressive muscle degeneration
leading to muscle atrophy, disability and death around the 2nd decade of
life. The mdx mouse has been widely studied as an animal model of DMD
since it also presents progressive muscle degeneration. In DMD and in the
mdx mouse, the disease is the result of the absence of the dystrophin
protein under the sarcolemma, which translates into membrane instability
against mechanical stimulation of muscle contraction and therefore fiber
disruption. It should be noted that in the mouse dystrophy is less severe than
in the child. Affected mice present an almost normal survival compared to
unaffected mice. Nevertheless, the amount of damage to the tissue depends
on the muscle group and this is why the diaphragm is the most damaged muscle
and the most comparable to that of sick children. In
recent years, the study of treatments for DMD by means of stem cell
transplantation has increased considerably. The possibility of modulating
the activity/bioavailability of growth factors (eg, IGF, myostatin) and
the use of drugs is also being studied. All these studies aim to recover
damaged muscle tissue and that is why the working model has focused on
myoblasts and myofibers. However, an aggravating factor of DMD is the
presence and progressive increase of muscle fibrosis. Fibroblasts residing
in fibrotic tissues are, to a large extent, responsible for the deposition
of extracellular matrix (ECM). In the presence of damage, they are capable
of activating what involves greater proliferation, MEC synthesis and the
acquisition of a contractile phenotype. Activation responds to various
stimuli including mechanical stress, hormones, and growth factors present
in damaged tissue. Among the latter, the most studied up to now is the
transforming growth factor type beta (TGF-beta) that is able to induce the
synthesis and deposit of MEC. The connective tissue growth factor (CTGF),
and very recently the growth factor derived from platelets type D (PDGF-D)
have also been studied. CTGF is present in different pathologies that
present with fibrosis but little is known about the role it plays in
skeletal muscle fibrosis. This factor responds to stimulation by TGF-13,
and it has been reported that both increase their expression in the muscle
tissue of the mdx mouse. However, the response to these factors in
fibroblasts isolated from skeletal muscle has not been reported. The study
of this cell group in muscular dystrophy is important since it is also a
target to be evaluated in therapies that favor muscle regeneration.
|
|---|
