Satellite Cell Specific p‐STAT3 Signalling in Human Muscle Following Acute Muscle Damage

Abstract

Interleukin 6 (IL6) acting through STAT3 is a known signalling cascade active in many cell types. Whether IL6 exclusively signals in satellite cells (SC) following acute myotrauma is unknown. Twelve male subjects (21 ± 2 y; 83 ± 12 kg) preformed 300 maximal muscle‐lengthening contractions of the quadriceps femoris at 180°·s−1 over a 55° range with muscle samples (vastus lateralis) and blood samples (antecubital vein) taken prior to exercise (PRE), 1h (T1), 3hrs (T3) and 24hrs (T24) post‐exercise. Cytosolic and nuclear fractions of muscle biopsies were purified and analyzed for total and p‐STAT3 using western blotting. P‐STAT3 was detected only in cytosolic fractions across the time course peaking at T24 (p<0.01 vs. PRE). Nuclear total and p‐STAT3 was not detected at any time point. However, immunohistochemical analysis revealed a progressive increase in the proportion of SC expressing p‐STAT3 with ~60% of all SC positive for p‐STAT3 at T24 (p<0.001 vs. PRE) and with cMyc, the production of which is regulated by p‐STAT3, detected in SC at T24. Whole muscle mRNA analysis revealed induction of the STAT3 target genes IL6, SOCS3, cMyc (peaking at T3, p<0.05), IL6Rα and GP130 (peaking at T24, p<0.05). Upregulation of these genes coupled with that of Myf5, (T24, p<0.05) with no appreciable change in MRF4, suggests that the IL6/STAT3 axis is active in promoting SC proliferation in the early phase following muscle damage in humans.