Regulation of type IV collagen gene expression and degradation in fast and slow muscles during dexamethasone treatment and exercise.

Glucocorticoids have anti-anabolic effects on many tissues and can cause muscle atrophy. However, their effects on type IV collagen gene expression and degradation in skeletal muscle have not been studied previously. Rats were treated daily with dexamethasone or saline. Half the groups of experimental and control animals were also subjected to daily endurance or uphill running exercise to determine the possible preventive effects of exercise. After an experimental period of 3 or 10 days, the extensor digitorum longus, soleus and tibialis anterior muscles were studied. Dexamethasone treatment for 10 days reduced muscle weight and type IV collagen mRNA abundance in all muscles. Gene expression of matrix metalloproteinase-2 (MMP-2) was decreased in fast muscles. However, the effects of this decrease were possibly attenuated by the simultaneous decrease in the activity of tissue inhibitor of metalloproteinases (TIMP-2). The amount of type IV collagen was not changed during dexamethasone treatment or exercise. The regulation of type IV collagen degradation during dexamethasone treatment varied between slow and fast muscles. Although endurance running prevented muscle atrophy, exercise could not compensate the changes observed in the regulation of type IV collagen gene expression and degradation during dexamethasone treatment.

Synthesis and degradation of type IV collagen in rat skeletal muscle during immobilization in shortened and lengthened positions.

AIM: Type IV collagen is a major protein in basement membranes surrounding and supporting skeletal muscle cells. In the present study, we tested the hypotheses that immobilization down-regulates synthesis and up-regulates degradation of type IV collagen in skeletal muscle. METHODS: mRNA level and concentration of type IV collagen as well as mRNA levels and activities of proteins involved in its degradation were analysed from soleus (SOL), gastrocnemius (GAS) and extensor digitorum longus muscles after immobilization in shortened and lengthened positions for 1, 3 and 7 days. RESULTS: Following immobilization, type IV collagen mRNA level was decreased in SOL and GAS suggesting down-regulated synthesis of this protein. The mRNA level and activity of matrix metalloproteinase-2 (proMMP-2) were increased in all muscles, while the activity of tissue inhibitor of metalloproteinase-2 was decreased in SOL and GAS. These findings reflect an increased capacity for degradation of type IV collagen. CONCLUSIONS: As a consequence of decreased synthesis/degradation ratio immobilization reduced the concentration of type IV collagen in all muscles. The regulation of type IV collagen through synthesis and/or degradation seems, however, to be muscle specific. Immobilization in lengthened position seems to delay and partly decrease the net degradation of type IV collagen.

Regulation of synthesis of fibrillar collagens in rat skeletal muscle during immobilization in shortened and lengthened positions.

Immobilization has been shown to cause muscle atrophy and decreased total collagen synthesis in skeletal muscle. These changes can be counteracted by stretch. The purpose of this study was to find out the early effects of immobilization in shortened and lengthened positions on expression of type I and III collagen at pre- and post-translational level. The mRNA levels of type I and III collagen, prolyl 4-hydroxylase activity, total collagen concentration and the proportions of type I and III collagens were analysed in soleus (SOL), gastrocnemius (GM), extensor digitorum longus and tibialis anterior (TA) muscles during immobilization in shortened and lengthened positions for 1, 3 and 7 days. The mRNA levels for type I and III collagens decreased during 3-7 days in all muscles, except TA. In shortened GM and SOL, the mRNA level of type I collagen was lower than in the corresponding lengthened muscles. Prolyl 4-hydroxylase activity decreased in all muscles during 3-7 days. The activity in shortened GM was 30-37% lower than in the lengthened one during 3-7 days. Total collagen concentration and proportions of type I and III collagen showed no change during the 7-day immobilization period. The present study suggests that immobilization results in rapid down-regulation of total muscular collagen synthesis and that the timing and degree is roughly similar in type I and III collagens. Stretch seems to partially counteract these effects. Immobilization effect and the partially preventive effect of stretch on down-regulation of gene expression of prolyl 4-hydroxylase and fibrillar collagens during immobilization seems to be greater in weight-bearing SOL and GM than ankle joint dorsiflexors.

Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content.

This experiment tested the hypothesis that running-induced damage to rat skeletal muscle causes changes in synthesis and degradation of basement membrane type IV collagen and to proteins regulating its degradation. Samples from soleus muscle and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or 1, 2, 4, or 7 days after downhill running. Increased muscle beta-glucuronidase activity indicated greater muscle damage in the red part of MQF than in the white part of MQF or soleus. In the red part of MQF, type IV collagen expression was upregulated at the pretranslational level and the protein concentration decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein that degrades type IV collagen, and tissue inhibitor of metalloproteinase-2 (TIMP-2), a protein that inhibits degradation, were increased in parallel both at mRNA and protein levels. Type IV collagen mRNA level increased in the white part of MQF and soleus muscle. The protein concentration increased in the white part of MQF and was unchanged in soleus muscle. MMP-2 and TIMP-2 changed only slightly in the white part of MQF and soleus muscle. The changes seem to depend on the severity of myofiber injury and thus probably reflect reorganization of basement membrane compounds.