Date of Award
Master of Science (MS)
Background: Although the satellite cell (SC) is a key regulator of muscle adaptation following exercise, the regulation of human muscle SC function in response to damaging exercise remains largely unexplored. STAT3 signalling, mediated via interleukin-6 (IL-6), has recently come to the forefront as a potential regulator of SC proliferation. The early response of the SC population in human muscle to muscle-lengthening contractions (MLC) as mediated by STAT3 has not been studied.
Methodology/Principal Findings: Twelve male subjects (21 ± 2 y; 83 ± 12 kg) performed 300 maximal MLC of the quadriceps femoris at a velocity of 180˚·s-1 over a
55° range of motion with muscle samples (vastus lateralis) and blood samples (antecubital vein) taken prior to exercise (PRE), 1 hour (T1), 3 hours (T3) and 24 hours (T24) post-exercise. Cytoplasmic and nuclear fractions of muscle biopsies were purified and analyzed for total and phosphorylated STAT3 (p-STAT3) by western blot. p-STAT3 was detected in cytoplasmic fractions across the time course, peaking at T24 (p<0.01 vs. PRE). Nuclear total and p-STAT3 were not detected at appreciable levels. However, immunohistochemical analysis revealed a progressive increase in the proportion of SCs expressing p-STAT3 with ~60% of all SCs positive for p-STAT3 at T24 (p<0.001 vs. PRE). Additionally, cMYC, a STAT3 downstream gene, was significantly up-regulated in SCs at T24 versus PRE (p<0.05). Whole muscle mRNA analysis revealed induction of the STAT3 target genes 1L-6, SOCS3, cMYC (peaking at T3, p<0.05), IL-6Rα and GP130 (peaking at T24, p<0.05). In addition, MYF5 mRNA was up-regulated at T24 (p<0.05) with no appreciable change in MRF4 mRNA.
Conclusions/Significant Findings: We have demonstrated that IL-6 mediated induction of STAT3 signaling occurred exclusively in the nuclei of SCs in response to MLC. An increase in the number of cMYC+ SCs indicated that human SCs were induced to proliferate under the control of STAT3 signaling.
Toth, Kyle G., "Satellite cell regulation in response to acute damaging lengthening contraction: Interleukin-6 mediated STAT3 induced proliferation" (2010). Open Access Dissertations and Theses. Paper 4303.
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