| Synthesis and degradation of muscle collagen during immobilization, glucocorticoid treatment and in neuromuscular diseases | ||
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The mRNA level of type I collagen was 180 % and type III collagen 139 % greater in patients with polymyositis compared to control subjects. Type I and III collagen mRNA levels were also elevated in polyneuropathy (a 66 % and 5 % increase, respectively). Immunohistochemistry revealed increased PINP, PIIINP and IIINTP staining intensities in the perimysium and endomysium of patients with polymyositis and polyneuropathy. In polyneuropathy, PINP was increased mostly in the endomysium, whereas PIIINP and IIINTP were elevated equally in both peri- and endomysium. No differences were observed between the myopathy patients and control subjects in the mRNA levels or immunohistochemical stainings of fibrillar collagens. Summary of the main results is presented in Table 4.
The mRNA level of type IV collagen was 118 % greater in polymyositis and 43 % greater in polyneuropathy patients compared to control subjects. The type IV collagen concentration (ng/mg wet weight) was 83 % higher in polyneuropathy (n=4) compared to controls. The immunohistochemical staining intensity for type IV collagen was increased around the muscle cells and capillaries in patients with polymyositis and polyneuropathy. No differences were observed between myopathy patients and control subjects in the mRNA level, protein concentration or staining intensity of type IV collagen.
The mRNA level of MMP-1 was 60 % higher in polymyositis compared to controls. The mRNA level of MMP-2 was 168 % elevated in polymyositis and 37 % elevated in polyneuropathy. No difference compared to controls was observed in proMMP-2 quantity (n=5) in muscles of patients with polyneuropathy, but the quantity of proMMP-9 (n=4) was 143 % elevated in this disease. Immunohistochemistry revealed more cells stained for MMP-9 in both polyneuropathy and polymyositis patients compared to control subjects. No differences in any of the MMP markers were observed between myopathy patients and control subjects.
Table 4. Summary of the main findings.
| Immob Short Length | Dexamethasone Sedent Exerc | Exercise | Neuropathy | Myositis | |||
|---|---|---|---|---|---|---|---|
| P 4-H | |||||||
| mRNA | ↓↓ | ↓ | |||||
| Activity | ↓↓ | ||||||
| Hyp | ↑ | | | |||||
| Coll I | |||||||
| mRNA | ↓ | −/↓ | ↑↑ | ↑↑↑ | |||
| PINP | ↑↑ | ↑↑↑ | |||||
| Coll III | |||||||
| mRNA | ↓↓ | ↓ | ↑↑ | ↑↑↑ | |||
| PIIINP | ↑↑ | ↑↑↑ | |||||
| Coll IV | |||||||
| mRNA | ↓↓ | ↓ | ↓↓↓ | ↓↓↓ | −/↑↑ | ↑↑ | ↑↑↑ |
| Conc. | ↓↓ | −/↓ | −/↑ | −/↑ | | | ↑↑ | |
| MMP-2 | |||||||
| mRNA | ↑↑ | ↑ | −/↓ | −/↓ | | | ↑ | ↑↑↑ |
| Protein | ↑↑ | −/↑ | ↓↓ | ↓↓ | | | | | |
| MMP-9 | ↑↑ | ||||||
| TIMP-1 | | | | | −/↓ | ||||
| TIMP-2 | ↓↓ | ↓ | ↓↓↓ | ↓ | −/↑ | ||
| Immob = immobilized; Short = shortened; Length = lengthened; Hyp = hydroxyproline; Conc = concentration; | = no change to control; ↑ or ↓ = slightly increased of decreased; ↑↑ or ↓ = increased or decreased; ↑↑↑ or ↓↓↓ = highly increased or decreased. | |||||||