Signal transducer and activator of transcription 3 signaling as a potential target to treat muscle wasting diseases

Curr Opin Clin Nutr Metab Care. 2016 May;19(3):171-6. doi: 10.1097/MCO.0000000000000273.

Abstract

Purpose of review: The review summarizes our current knowledge of the role of signal transducer and activator of transcription 3 (STAT3) signaling in skeletal muscle regeneration and the maintenance of muscle mass.

Recent findings: STAT3 signaling plays a pivotal role in regulating the function of multiple cell types in skeletal muscle. This includes muscle stem cells, myofibers, and macrophages. It regulates muscle stem cell function by antagonizing self-renewal. STAT3 also functions in myofibers to regulate skeletal muscle mass. This is highly relevant under pathological conditions where STAT3 activation promotes protein degradation and muscle atrophy. Transient pharmacological inhibition of STAT3 partially prevents muscle wasting. However, the mechanisms responsible for the improvement of muscle condition are not currently well understood. This is because of the complexity of the system, as STAT3 has a critical role in regulating the function of several cell types residing in skeletal muscle.

Summary: Muscle wasting is associated with several human diseases such as muscle dystrophies or cancer cachexia. However, currently there are no effective treatments for this condition, and there is a critical need to identify new potential targets for the development of efficient therapeutic approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Adult Stem Cells / cytology
  • Adult Stem Cells / drug effects
  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / pathology
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Self Renewal* / drug effects
  • Humans
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Models, Biological*
  • Molecular Targeted Therapy
  • Muscle Development* / drug effects
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Disorders, Atrophic / drug therapy
  • Muscular Disorders, Atrophic / immunology
  • Muscular Disorders, Atrophic / metabolism
  • Muscular Disorders, Atrophic / pathology
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism*
  • Wasting Syndrome / drug therapy
  • Wasting Syndrome / immunology
  • Wasting Syndrome / metabolism
  • Wasting Syndrome / pathology

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human