Synthesis and Degradation of Muscle Collagen during Immobilization, Glucocorticoid Treatment and in Neuromuscular Diseases

To investigate the turnover of type IV collagen in skeletal muscle in conditions where muscle function is impaired, type IV collagen and proteins regulating its degradation were studied during 1, 3 and 7 days of immobilization, 3and 10-day glucocorticoid treatment and in neuromuscular diseases. In addition, fibrillar type I and III collagens were studied during immobilization and in neuromuscular diseases. The mRNA levels of type I, III and IV collagens were decreased during immobilization and during 10-day dexamethasone treatment. Gene expression and quantity of (pro)MMP-2 was increased during immobilization but decreased during dexamethasone treatment. The expression of TIMP-2 was decreased both during immobilization and dexamethasone treatment. Decreased gene expression and increased degradation caused decreased concentration of type IV collagen, suggesting net degradation of type IV collagen during immobilization. While the gene expression and degradation were decreased during dexamethasone treatment, the amount of type IV collagen was not changed. Dexamethasone thus seemed to slow down the turnover of type IV collagen. Decreased mRNA levels of collagens and prolyl 4-hydroxylase suggest decreased biosynthesis of collagens during immobilization. The mRNA levels of collagens I, III and IV were increased in polyneuropathy and polymyositis. The concentration and staining intensity of type IV collagen was increased in polyneuropathy, as was also the quantity and staining intensity of (pro)MMP-9. The results suggest accumulation of type IV collagen in the basement membranes of muscle cells and capillaries in polyneuropathy muscles. Lengthened position during immobilization partly prevented the atrophy and changes in collagen metabolism in plantarflexors. Endurance running was effective in preventing muscle atrophy during dexamethasone treatment, but exercise did however fail to prevent the changes observed in type IV collagen synthesis and degradation.