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Comparison of basic fibroblast growth factor in X-linked dystrophin-deficient myopathies of human, dog and mouse
J E Anderson1, B A Kakulas, P F Jacobsen
1Department of Anatomy, University of Manitoba, Winnipeg, Canada.
Abstract:
Binding of polyclonal antibodies specific for bFGF was examined in tissue sections of myopathic and normal muscles from humans, dogs and mice. The proposal tested was that differences in the amount or distribution of bFGF in muscles of the 3 species, might correlate with the limited muscle regeneration seen in humans and dogs afflicted with x-linked muscular dystrophy, in contrast with the sustained new muscle formation in mdx mice with the homologous myopathy. There was a striking difference between the species in the binding of bFGF antibodies to extracellular matrix, particularly at the periphery of myofibres; binding was pronounced in mouse but weak or absent in human and dog muscle. Binding to muscle nuclei and sarcoplasm was also stronger in mice than in humans and dogs, and in all species was more pronounced in foetal than adult muscle. Increased binding of bFGF antibodies was seen in damaged and regenerating muscle cells in all myopathic specimens where these were present. This was associated with the regenerative process rather than with myopathy, as a similar pattern of bFGF expression was seen in mouse muscle regenerating after experimental crush injury. The higher extracellular staining for bFGF around the periphery of mouse myofibres correlated with the successful muscle regeneration in dystrophic mice. Results suggest that bFGF at the fibre periphery might stimulate a local increase in the numbers of muscle precursor cells which can respond to injury in the mdx mouse.
Insights
Differences in basic fibroblast growth factor (bFGF) distribution in muscle correlate with regeneration capacity across species. Mouse muscle shows higher bFGF binding, linked to successful regeneration in muscular dystrophy.
Area of Science:
- Muscle regeneration
- Cellular biology
- Biochemistry
Background:
- Muscular dystrophies in humans and dogs show limited regeneration compared to mdx mice.
- Basic fibroblast growth factor (bFGF) is implicated in cellular growth and repair.
Purpose of the Study:
- To investigate the role of bFGF distribution in species-specific muscle regeneration differences.
- To correlate bFGF levels with the varying regenerative capacities observed in human, dog, and mouse muscular dystrophies.
Main Methods:
- Immunohistochemical analysis of bFGF antibody binding in muscle tissue sections from humans, dogs, and mice.
- Comparison of bFGF distribution in normal, myopathic, fetal, and adult muscle across species.
- Examination of bFGF expression patterns in regenerating muscle following injury.
Main Results:
- Species-specific differences in bFGF antibody binding were observed, notably in the extracellular matrix and myofiber periphery.
- Mouse muscle exhibited significantly stronger bFGF binding compared to human and dog muscle.
- Increased bFGF binding was associated with muscle regeneration, not solely with myopathy, and was more pronounced in fetal and regenerating tissues.
Conclusions:
- Higher extracellular bFGF at the myofiber periphery in mice correlates with successful muscle regeneration in dystrophic models.
- bFGF at the fiber periphery may enhance muscle precursor cell proliferation, aiding injury response in mdx mice.
- Species-specific bFGF distribution influences the differential capacity for muscle regeneration.