Discovery of thymosin β4 as a human exerkine and growth factor

Am J Physiol Cell Physiol. 2021 Nov 1;321(5):C770-C778. doi: 10.1152/ajpcell.00263.2021. Epub 2021 Sep 8.

Abstract

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in the plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.

Keywords: exercise; exerkine; growth factor; muscle contraction; secreted factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Models, Animal
  • Humans
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Contraction*
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology
  • Muscular Diseases / physiopathology
  • Neuronal Outgrowth / drug effects*
  • Osteoblasts / drug effects*
  • Osteoblasts / pathology
  • Physical Endurance
  • Proteomics
  • Signal Transduction
  • Tandem Mass Spectrometry
  • Thymosin / metabolism*
  • Thymosin / pharmacology*

Substances

  • thymosin beta(4)
  • Thymosin

Associated data

  • figshare/10.6084/m9.figshare.c.5602545