Markers of degeneration and regeneration in Duchenne muscular dystrophy.
Dystrophin deficiency associated with Duchenne muscular dystrophy (DMD) results in chronic inflammation and severe skeletal muscle degeneration, where the extent of muscle fibrosis contributes to disease severity. The microenvironment of dystrophic muscles is associated with variation in levels of markers of degeneration and regeneration. Since in dystrophic muscle apoptosis precedes necrosis, markers of apoptosis can be used as indicators of degeneration, while regeneration can be measured in terms of cytokines and growth factor expression"; and then throughout the text use "markers of apoptosis/degeneration. The present study is an attempt to evaluate the extent of degeneration and regeneration in DMD patient blood. Subjects were 24 boys with DMD diagnosed at the molecular level versus 20 age and socioeconomic matching healthy boys. In their blood, levels of Fas and FasL and Bax/Bcl-2 and plasma DNA fragmentation were measured as markers of apoptosis. The cytokine tumor necrosis factor alfa (TNF-alpha), and the growth factors: basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were measured as markers of regeneration. Plasma DNA fragmentation (0.38% +/- 0.12 vs. 0.2% +/- 0.15) and Fas (9.9 +/- 2.8 vs. 2 +/- 0.1, p < 0.001) together with FasL mRNA expression in circulating lymphocytes (0.47 +/- .09 vs. 0.24 +/- .04, p < 0.001) were significantly increased in DMD patients compared to controls. There was a significant increase in Bax (0.19 +/- 0.7 vs. 0.05 +/- 0.1, p < 0.00001) expression and a significant decrease in Bcl-2 protein (6.4 +/- 1.6 vs 10 +/- 2.8, p < 0.00001) as compared to controls. Among markers of regeneration, TNF- alpha (30.2 +/- 9.5 vs. 3.6 +/- 0.9) and bFGF (21.7 +/- 10.3 vs. 4.75 +/- 2.2) were significant increased while VEGF was significantly decreased (190 +/- 115 vs. 210 +/- 142.) in blood of DMD patients compared to controls. Our results indicate that Fas/FasL and Bax/Bcl-2 are involved in muscle atrophy and degeneration in DMD patients, while regeneration process does not cope with the degeneration.
Abdel-Salam
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Department of Pediatrics, Genetics Unit, Faculty of Medicine, Cairo University. ekab@link.net
Abdel-Meguid
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Korraa
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D017209:Apoptosis; D002648:Child; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000097:blood
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D016222:Fibroblast Growth Factor 2