Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle.

Journal Article (Journal Article)

Chronic inflammatory diseases often lead to muscle wasting and contractile deficit. While exercise can have anti-inflammatory effects, the underlying mechanisms remain unclear. Here, we used an in vitro tissue-engineered model of human skeletal muscle ("myobundle") to study effects of exercise-mimetic electrical stimulation (E-stim) on interferon-γ (IFN-γ)-induced muscle weakness. Chronic IFN-γ treatment of myobundles derived from multiple donors induced myofiber atrophy and contractile loss. E-stim altered the myobundle secretome, induced myofiber hypertrophy, and attenuated the IFN-γ-induced myobundle wasting and weakness, in part by down-regulating JAK (Janus kinase)/STAT1 (signal transducer and activator of transcription 1) signaling pathway amplified by IFN-γ. JAK/STAT inhibitors fully prevented IFN-γ-induced myopathy, confirming the critical roles of STAT1 activation in proinflammatory action of IFN-γ. Our results reveal a previously unknown mechanism of the cell-autonomous anti-inflammatory effects of muscle exercise and establish the utility of human myobundle platform for studies of inflammatory muscle disease and therapy.

Full Text

Duke Authors

Cited Authors

  • Chen, Z; Li, B; Zhan, R-Z; Rao, L; Bursac, N

Published Date

  • January 22, 2021

Published In

Volume / Issue

  • 7 / 4

PubMed ID

  • 33523949

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

International Standard Serial Number (ISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abd9502


  • eng