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

Abstract

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.

Role of Exercise Therapy in Prevention of Decline in Aging Muscle Function: Glucocorticoid Myopathy and Unloading

“…The downregulation of collagen synthesis during dexamethasone administration shows that ECM components decrease [44]. As shown previously [38], MyHC synthesis rate only decreased in FT muscles, while the expression of collagen I, III, and IV mRNA decreased in both FT and slow-twitch (ST) muscles.…”

“…An excess of glucocorticoids has some similarities in its effect on the intracellular and extracellular compartments of skeletal muscle, for example, the decreased synthesis of proteins [34, 44]. The downregulation of collagen synthesis during dexamethasone administration shows that ECM components decrease [44].…”

Near Infrared Spectroscopy (NIRS) as a New Non-Invasive Tool to Detect Oxidative Skeletal Muscle Impairment in Children Survived to Acute Lymphoblastic Leukaemia

“…A limitation of the capacity of muscle fibres to consume O 2 in leukaemia survivors may be explained at least in part by muscle atrophy due to the catabolic effects of malignancy treatment such as vincristine or corticosteroids. Glucocorticoids inhibit overall protein synthesis in skeletal muscle causing muscle atrophy and loss of muscle function, the effect of corticosteroids being to blunt the stimulatory effect of insulin and amino acids on protein synthesis [14], [15]. Also, the muscle connective tissue undergoes a gene suppression leading to a collagen degradation, especially in fast muscles [14].…”

“…An additional explanation is that muscle atrophy and altered muscle function may be further worsened by bed rest and sedentary habits [5]. Although aerobic activities could prevent muscle atrophy, exercise may not to be able to compensate for the changes observed during corticosteroid treatment [15]. As a result, when physical exercise is kept low, muscle atrophy and early fatigue become self-perpetuating conditions [6].…”

Remodelling of Skeletal Muscle Extracellular Matrix: Effect of Unloading and Reloading

“…Laminin and type IV collagen are connected to each other by nidogen-1 in the muscular basement membranes [2,19]. As a part of the flexible basement membrane, type IV collagen network is interconnected with other extracellular matrix compounds and sarcolemmal proteins, being consequently exposed to stretching effects during muscle contraction [20,21]. The formation process of type IV collagen is demonstrated in Figure 2.…”