The effect of acute and long-term physical activity on extracellular matrix and serglycin in human skeletal muscle

Remodeling of extracellular matrix (ECM), including regulation of proteogly-cans in skeletal muscle can be important for physiological adaptation to exercise. To investigate the effects of acute and long-term exercise on the expression of ECM-related genes and proteoglycans in particular, 26 middle-aged, sedentary men underwent a 12 weeks supervised endurance and strength training intervention and two acute, 45 min bicycle tests (70% VO(2)max), one at baseline and one after 12 weeks of training. Total gene expression in biopsies from m. vastus lateralis was measured with deep mRNA sequencing. After 45 min of bicycling approximately 550 gene transcripts were >50% upregulated. Of these, 28 genes (5%) were directly related to ECM. In response to long-term exercise of 12 weeks 289 genes exhibited enhanced expression (>50%) and 20% of them were ECM related. Further analyses of proteoglycan mRNA expression revealed that more than half of the proteoglycans expressed in muscle were significantly enhanced after 12 weeks intervention. The proteoglycan serglycin (SRGN) has not been studied in skeletal muscle and was one of few proteoglycans that showed increased expression after acute (2.2-fold, P < 0.001) as well as long-term exercise (1.4-fold, P < 0.001). Cultured, primary human skeletal muscle cells expressed and secreted SRGN. When the expression of SRGN was knocked down, the expression and secretion of serpin E1 (SERPINE1) increased. In conclusion, acute and especially long-term exercise promotes enhanced expression of several ECM components and proteoglycans. SRGN is a novel exercise-regulated proteoglycan in skeletal muscle with a potential role in exercise adaptation.