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

Abstract

Remodeling of extracellular matrix (ECM), including regulation of proteoglycans 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% VO2max), 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.

Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

“…EPS increased the expression of PPARGC1A and IL6 , 1.3- and 3-fold, respectively, as previously shown [27]. However, only CSF1 was significantly up-regulated by 24 h EPS (1.3-fold, p < 0.05), whereas FAM20C expression was reduced −1.25-fold (p < 0.05).…”

“…LAMB1 , SPARC , NID1 and ELN ). Some of these data were recently reported and discussed in another publication [27].…”

“…Correction for multiple testing was performed by using Benjamini-Hochbergs false discovery rate (FDR) control [26], set at FDR < 10%. The dataset generated from RNA-seq has been used in several other publications, including one study where gene expression data for extracellular matrix (ECM) genes were reported [27]. To compare our data on CSF1 with other published data sets on skeletal muscle and exercise, we analyzed two data sets [28], [29].…”

“…Myoblasts were proliferated to passage 4–5 and differentiated [27]. EPS (1 Hz, 2 ms, 11.5 V) was applied to the cells after 5 days of differentiation for 24 h or after 6 days of differentiation for 1–6 h. EPS should mimic muscle contraction similar to in vivo exercise [32].…”

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

“…Collagen immunoreactivity was assessed within tissue regions located distant to the repair/defect site, while the tissue used for PCR analysis was collected from the repair site. As a result, the collagen immunoreactivity measures are likely an indicator of tissue wide ECM adaptation to differences in force generation and transmission between treatment groups, 44 while the PCR results are indicative of the regenerative and remodeling processes occurring at the site of repair.…”