Activation of Satellite Cells Following Eccentrically-Biased Exercise in Humans

Abstract

<p> We aimed to examine the satellite cell response and the potential of HGF signaling in mediating satellite cell activation and proliferation. To achieve this, we determined the time course of satellite cell activation and expression of HGF, HGFA, HAI-l, HAI-2 and the MRFs in skeletal muscle, as well as HGF protein in the blood, before and over five days following an acute bout of eccentrically-biased exercise. Eight recreationally active participants (20.6 ± 2.1 y; 180.5 ± 5.2 cm; 81.4 ± 9.8 kg) were recruited for the study. Subjects were required to perform 300 eccentric contractions involving the quadriceps femoris muscles at 180 °/s, over a 60° range of motion with a randomly selected leg. A baseline biopsy (PRE) was taken from the opposite leg. Muscle and blood samples were taken before the exercise (PRE) and at 4 h (T4), 24 h (T24), 72 h (T72) and 120 h (T120) following the exercise. The exercise protocol resulted in an increase in the number of satellite cells (N-CAM labeled cells), expressed both relative to myofiber number and relative to total myonuclei, between PRE and T4 which was sustained over the time course (p<0.001). Further increases in N-CAM labeled cells, expressed relative to myofibre cross-section, were observed between T4 and T24 (p=0.01) and between T4 and T72 (p=0.002). Myf5 mRNA expression increased significantly from both PRE and T4 by T24 (p=0.04). MyoD mRNA increased significantly from PRE by T4 (p=0.02). Myogenin mRNA increased significantly at T24 versus PRE (p=0.02). No significant change was observed over time for MRF4. HGF protein increased significantly in serum from baseline (PRE) to T4 (p=0.04). Active HGF protein was detected in skeletal muscle at rest (14.4±1.3 avg IDV/actin avg IDV) and tended to increase from PRE to T24 (p=0.12). HGFA protein increased significantly from PRE to T24 (p=0.04). HAI-2 increased significantly from PRE at T72 (p=0.03) and T120 (p=0.04). HAI-1 protein increased significantly from PRE to T24 (p=0.02). HAI-2 (32 kDa) increased significantly from baseline (PRE) by T24 (p=0.03), and also by T72 and T120 (p=0.02). HAI-2 (28 kDa) protein showed no significant change over time HGF, HGFA, HAI-1, and HAI-2 transcripts were undetected over the time course. We conclude that a single bout of high-intensity exercise is sufficient to activate satellite cells, which may involve both a local and systemic response to exercise-induced injury. Furthermore, we propose that HGF signaling plays an important role in the regulation of satellite cells in the post exercise period.</p>