Hepatocyte Growth Factor Signaling in Mediating Human Muscle Satellite Cell Activation and Proliferation Following Eccentric Exercise

Abstract

Eight subjects (20.6 ± 2.1 yr; 81.4 ± 9.8 kg) performed 300 isolateral eccentric contractions (knee extensions at 180 °/s) to evaluate the skeletal muscle satellite cell (SC) response and the potential of hepatocyte growth factor (HGF) signaling in mediating SC activation and proliferation following acute damaging exercise. Muscle biopsies were obtained from the vastus lateralis of the non‐exercised leg prior to exercise (PRE) and the exercised leg at 4 (T4), 24 (T24), 72 (T72), and 120 h (T120) post‐exercise. The number of SC (N‐CAM+) increased (p < 0.001) by T4 and remained elevated at T120 (p = 0.002). Serum HGF increased at T4 (p < 0.05) with a trend for increased muscle HGF and HGF activator (HGFA) protein expression at T24 with active HGF detected in all PRE samples. HGFA inhibitors (HAI‐1 and HAI‐2) protein content increased at T72 and remained elevated at T120 (p < 0.05). Myogenic regulatory factors (MyoD and Myf5) mRNA expression increased at T4 and T24 (p < 0.05) respectively, with increased myogenin mRNA expression at T24 (p < 0.05). Furthermore, plasma interleukin‐6 concentration increased ∼200% (p < 0.05) by T4, illustrating a roll of both local and systemic signaling in the activation and proliferation of SC; with HGF signaling playing an important regulatory role in the SC response to exercise‐induced muscle damage.Supported by NSERC