Interleukin‐6 Signaling Mediates Human Muscle Satellite Cell Proliferation Following Acute Muscle Damage
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abstract
Interleukin‐6 (IL‐6) has been implicated in satellite cell (SC)‐mediated muscle hypertrophy in animals; however, the role of IL‐6 in the SC response to acute injury in humans remains to be elucidated. Eight subjects (22 ± 1 y; 79 ± 8 kg) performed 300 maximal leg lengthening contractions (3.14 rad.s−1). Blood and muscle samples were collected before and at 4 (T4), 24 (T24), 72 (T72), and 120 hr (T120) post intervention. IL‐6, IL‐6 receptor (IL‐6R), Cyclin D1, SOCS3 mRNA and serum IL‐6 protein were measured. JAK2 and STAT3 phosphorylated and total protein and immunohistochemistry for phosphorylated STAT3 (p‐STAT3), IL‐6 and Pax7 were analyzed across all time‐points. Serum IL‐6 increased 200% by T4, while IL‐6 mRNA increased 4.5‐fold at T4, and IL‐6R mRNA increased 5‐fold at T4. Serum IL‐6 strongly correlated to muscle IL‐6 mRNA (r2 = 0.89, p = 0.02). The number of Pax7+ cells (% myonuclei) increased 74% at T24, peaking at T72 (157% increase from PRE). SC that were IL‐6+ (% of Pax7+ cells) increased from 2% at PRE, to 60% at T4 and peaked at T24 (80% of SC). By T72, IL‐6+ SC dropped to PRE values. There was no change in JAK2, p‐JAK2, STAT3 or p‐STAT3 whole muscle protein; however, p‐STAT3 localized to the SC at T4. Cyclin D1 increased T4 and T24 (6‐fold), and SOCS3 increased 6‐fold at T24. These data suggest that IL‐6, signaling via the JAK/STAT3 pathway, mediates SC proliferation following acute myotrauma in humans.Supported by NSERC
