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The cell surface receptor Fn14/TWEAKR was recently reported by our laboratory to be a prominent marker in the resistance exercise (RE) induced Transcriptome. The purpose of the present study was to extend our Transcriptome findings and investigate the gene and protein expression time course of markers in the TWEAK-Fn14 pathway following RE or run exercise (RUN). Vastus lateralis muscle biopsies were obtained from 6 RE subjects [25 ± 4 yr, 1-repetition maximum (RM): 99 ± 27 kg] pre- and 0, 1, 2, 4, 8, 12, and 24 h post RE (3 × 10 at 70% 1-RM). Lateral gastrocnemius biopsies were obtained from 6 RUN subjects [25 ± 4 yr, maximum oxygen uptake (V̇O2max): 63 ± 8 ml·kg(-1)·min(-1)] pre- and 0, 1, 2, 4, 8, 12, and 24 h after a 30-min RUN (75% V̇O2max). After RE, Fn14 gene and protein expression were induced (P &lt; 0.05) and peaked at 8 and 12 h, respectively. Downstream markers analyzed showed evidence of TWEAK-Fn14 signaling through the alternative NF-κB pathway after RE. After RUN, Fn14 gene expression was induced (P &lt; 0.05) to a much lesser extent and peaked at 24 h. Fn14 protein expression was only measurable on a sporadic basis, and there was weak evidence of alternative NF-κB pathway signaling after RUN. TWEAK gene and protein expression were not influenced by either exercise mode. These are the first human data to show a transient activation of the TWEAK-Fn14 axis in the recovery from exercise, and our data suggest the level of activation is exercise mode dependent. Furthermore, our collective data support a myogenic role for TWEAK-Fn14 through the alternative NF-κB pathway in human skeletal muscle.

TWEAK-Fn14 pathway activation after exercise in human skeletal muscle: insights from two exercise modes and a time course investigation