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Basic fibroblast growth factor and muscular dystrophy.

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LETTERS
Basic Fibroblast Growth
Factor and Muscular
Dystrophy
myopathies of human, dog and mouse. Growth Factors 1993;9:
107-121
3. Matsuda S , Desaki J, Fujita H , et al. Immuno-electronmicroscopic localization of basic fibroblast growth factor in the
dystrophic mdx mouse masseter muscle. Cell Tissue Res 1992;
J. P. Lefaucheur, MD, and A. Skbille, M D
4. DiMario J, Strohman RC. Satellite cells from dystrophic (rndx)
We read with interest the findings of D r DAmore and associates [I] that basic fibroblast growth factor (bFGF) levels are
abnormally elevated in the sera of patients with Duchenne
muscular dystrophy (DMD). The authors indicate that these
increased bFGF levels may be induced by the chronic release
of bFGF, as a consequence of rhe reduced plasma membrane
stability of dystrophin-deficient muscles. Although mdx mice
exhibit dystrophin deficiency, bFGF is undetectable in the
sera of mdx mice. The elevation of bFGF levels is suggested
to result in the fibrosis early observed in the muscles of
D M D patients.
In mdx mice some data suggest that bFGF is involved in
the muscle regeneration and not in fibrosis. Anderson and
co-workers {23 showed that the binding of bFGF antibodies
to the extracellular matrix of myofibers was pronounced in
mdx mice, but weak or absent in D M D patients. Considerable amounts of bFGF were also seen into the cytoplasm of
regenerating myocytes in mdx muscles by use of immunohistochemistry [3]. O n the other hand, the bFGF-induced cell
proliferation in vitro seemed to be heightened in the case of
mdx satellite cells, compared with fibroblasts or satellite cells
of other species [43. At least we observed a positive correlation between the number of regenerating fibers and the concentration of bFGF injected in muscles of 4-week-old mdx
mice (unpublished data), since the injection of bFGF did not
enhance the regeneration of injured muscles in Swiss mice
E5l.
Muscle regeneration is successful in dystrophin-deficient
mdx mice, but not in D M D patients, and bFGF may be
increasingly available in mdx muscle, both stored into the
cytoplasm and sequestered by binding sites in the extracellular matrix or the plasma membrane. Thus, one may hypothesize that the local release of bFGF, either following the degradation of extracellular matrix or the disruption of plasma
membrane, promotes regeneration rather than fibrosis in dystrophin-deficient muscle. The poor muscle regeneration observed in D M D may result from a local deficiency in bFGF
availability, e.g., a failure in the binding to extracellular matrix, and this hypothesis may explain the elevation of bFGF
levels in the serum of D M D patients, which is not observed
in mdx mice.
Lboratoire de Physiologie
Facult6 de Midecine Saint-Antoine
27 rue Chaligny
75571 Paris cedex 12, France
References
1. DAmore PA, Brown R H Jr, Ku PT,et al. Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy. Ann Neurol 1994;35:362-365
2. Anderson JE, Kakulas BA, Jacobsen PF, et al. Comparison of
basic fibroblast growth factor in X-linked dystrophin-deficient
800
270:569-576
mouse muscle are stimulated by fibroblast growth factor in vitro.
Differentiation 1988;39:42-49
5. Lefaucheur JP, SCbille A. The basic fibroblast growth factorsaporin mitotoxin impairs in vivo skeletal muscle regeneration
following injury. Neuromusc Disord 1993;3:367-3 70
Reply
Patricia A. DAmore, PhD,* and Eric P. Hoffman, MDf
It is with considerable encouragement that we read the comments of Drs Lefaucheur and Skbille, which support our
findings, and those of two more recently published studies
from our laboratories, which continue studies in the possible
pathophysiological sequelae of dystrophin deficiency [I, 21.
In these newer studies, we hypothesize that muscle basic
fibroblast growth factor (bFGF) may be modulated differently in the muscle of dystrophin deficient humans (DMD)
and mice (mdx) due to differences in the biology and status
of mast cells in the two species. Indeed, the “local release of
bFGF’ hypothesized by Drs Lefaucheur and Skbiile may
most easily be achieved by local release of heparin by muscle
mast cells. Future studies must address the specific role of
bFGF in the successful regeneration of mdx mouse muscle,
and the extensive fibrosis seen in human D M D muscle: it is
likely involved in both.
+Laboratoryfo. Surgical Research
Children’s Hospital
Boston, M A 02115
?Department of Molecular Genetk and Biochemistry
Universitjl of Pittsburgh School of Medicine
Pittsburgh, PA 15261
References
1. Gorospe JRM, Tharp MD, Hinckley J, et al. A role for mast cells
in the progression of Duchenne muscular dystrophy? Correlations in dystrophin-deficient humans, dogs, and mice. J Neurol
Sci 1994;122:44-56
2. Gorospe JRM, Tharp MD, Demitsu T, Hoffman EP. Dystrophindeficient myofibers are vulnerable to mast cell necrosis. Neuromusc Disord 1994;4:325-334
Reduced Glucose
Transporter Concentrations
in Brains of Patients with
Alzheimer’s Disease
Ian A. Simpson, PhD,* and Peter Davies, PhDi
In an Editorial [I] that preceded our study in Annals [2],
D r Pardridge raises some points that he suggests we have
Copyright 0 1994 by the American Neurological Association
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