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

Publication ,  Journal Article
Chen, Z; Li, B; Zhan, R-Z; Rao, L; Bursac, N
Published in: Science advances
January 2021

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.

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Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

January 2021

Volume

7

Issue

4

Start / End Page

eabd9502

Related Subject Headings

  • Tissue Engineering
  • Signal Transduction
  • Muscle, Skeletal
  • Janus Kinases
  • Janus Kinase Inhibitors
  • Interferon-gamma
  • Humans
  • Exercise
  • Electric Stimulation
 

Citation

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Chen, Z., Li, B., Zhan, R.-Z., Rao, L., & Bursac, N. (2021). Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle. Science Advances, 7(4), eabd9502. https://doi.org/10.1126/sciadv.abd9502
Chen, Zhaowei, Binjie Li, Ren-Zhi Zhan, Lingjun Rao, and Nenad Bursac. “Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle.Science Advances 7, no. 4 (January 2021): eabd9502. https://doi.org/10.1126/sciadv.abd9502.
Chen Z, Li B, Zhan R-Z, Rao L, Bursac N. Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle. Science advances. 2021 Jan;7(4):eabd9502.
Chen, Zhaowei, et al. “Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle.Science Advances, vol. 7, no. 4, Jan. 2021, p. eabd9502. Epmc, doi:10.1126/sciadv.abd9502.
Chen Z, Li B, Zhan R-Z, Rao L, Bursac N. Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle. Science advances. 2021 Jan;7(4):eabd9502.

Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

January 2021

Volume

7

Issue

4

Start / End Page

eabd9502

Related Subject Headings

  • Tissue Engineering
  • Signal Transduction
  • Muscle, Skeletal
  • Janus Kinases
  • Janus Kinase Inhibitors
  • Interferon-gamma
  • Humans
  • Exercise
  • Electric Stimulation