Discovery of thymosin β4 as a human exerkine and growth factor

Alba Gonzalez-Franquesa, Ben Stocks, Melissa L. Borg, Michael Kuefner, Emilie Dalbram, Thomas S. Nielsen, Ankita Agrawal, Stanislava Pankratova, Alexander V. Chibalin, Håkan K.R. Karlsson, Sevda Gheibi, Marie Björnholm, Niklas Rye Jørgensen, Christoffer Clemmensen, Morten Hostrup, Jonas T. Treebak, Anna Krook, Juleen R. Zierath, Atul S. Deshmukh

Research output: Contribution to journalArticlepeer-review

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 b4 (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.

Original languageEnglish
Pages (from-to)C770-C778
JournalAmerican Journal of Physiology - Cell Physiology
Volume321
Issue number5
DOIs
Publication statusPublished - 2021 Nov 1

Subject classification (UKÄ)

  • Physiology and Anatomy

Free keywords

  • Exercise
  • Exerkine
  • Growth factor
  • Muscle contraction
  • Secreted factor

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