Heat stress promotes extracellular matrix remodelling via TGF-β1 and MMP-2/TIMP-2 modulation in tenotomised soleus and plantaris muscles

Purpose: Heat stress has been shown to reduce muscle atrophy and enhance muscle regeneration. However, the role of heat stress on extracellular matrix (ECM) remodelling remains poorly understood. Here, we examined the effect of heat exposure on intramuscular fibrosis and its associated signalling in soleus and plantaris muscles after tenotomy. Materials and methods: Male Wistar rats were randomly divided into four groups: sedentary control (CON), control plus heat stress (CON+HEAT), tenotomy (TEN) for 8 days, and tenotomy for 8 days plus heat stress (TEN+HEAT). Whole body heat stress was maintained at 40.5-41.5 °C for 30 min, 24 h before and 1-6 days after tenotomy. Results: Tenotomy resulted in muscle atrophy and a substantial increase in intramuscular collagen content, which was more pronounced in soleus than in plantaris muscles, whereas laminin content remained unaffected. These effects were associated with increases in MMP-2 activity, TIMP-2, and TGF-β1 protein expressions. Heat stress, however, attenuated tenotomy-induced intramuscular collagen accumulation in soleus muscle and reduced TIMP-2 and TGF-β1 protein expressions, but had no effect on MMP-2 activity in both muscles. These alterations were concomitant with the induction of heat shock protein 72 (Hsp72). Conclusion: These data demonstrated that heat stress could reduce intramuscular fibrosis, at least in part, through decreasing TGF-β1 and TIMP-2 protein expressions of tenotomised soleus muscle. The results from this study shed light on the mechanism and suggest the potential therapeutic effect of heat stress in alleviating intramuscular fibrosis after tenotomy.