Discovery of thymosin β4 as a human exerkine and growth factor.
Alba Gonzalez-FranquesaBen StocksMelissa L BorgMichael KuefnerEmilie DalbramThomas S NielsenAnkita AgrawalStanislava PankratovaAlexander V ChibalinHåkan K R KarlssonSevda GheibiMarie BjörnholmNiklas Rye JørgensenChristoffer ClemmensenMorten HostrupJonas T TreebakAnna KrookJuleen R ZierathAtul Shahaji DeshmukhPublished in: American journal of physiology. Cell physiology (2021)
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.
Keyphrases
- growth factor
- insulin resistance
- mass spectrometry
- skeletal muscle
- high fat diet induced
- endothelial cells
- metabolic syndrome
- adipose tissue
- type diabetes
- induced pluripotent stem cells
- liquid chromatography
- stem cells
- pluripotent stem cells
- high fat diet
- machine learning
- small molecule
- multiple sclerosis
- high resolution
- gas chromatography
- deep learning
- weight gain
- weight loss
- capillary electrophoresis
- combination therapy
- amino acid
- protein protein