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Tissue biology · Thymosin β4 / TB-500

Thymosin β4 in mouse cardiac injury models

October 22, 2026 · 1 min read · Models: Mouse, Cell culture

Thymosin β4 is a 43-amino-acid actin-sequestering protein. Two landmark mouse studies in Nature linked it to cardiomyocyte survival and to the activation of epicardial progenitor cells after injury. “TB-500” usually refers to a synthetic peptide based on its actin-binding region.

A summary of published research for scientific reference. It is not medical advice and does not describe or endorse use in humans or animals. Findings from cell culture and animal models often do not carry over to other systems.

An actin-binding protein with signaling roles

Thymosin β4 (Tβ4) is one of the most abundant intracellular peptides in mammalian cells. It binds monomeric G-actin and regulates the pool available for filament assembly, so it affects cell motility. Its actin-binding motif (centered on the sequence LKKTETQ) is the basis of the shorter synthetic peptides marketed to researchers as TB-500.

Landmark studies

Bock-Marquette and colleagues (Nature, 2004) reported that Tβ4 activates integrin-linked kinase (ILK) and Akt in cardiomyocytes. In a mouse coronary ligation model, they measured infarct size and cardiac function in mice given Tβ4 and linked the results to ILK–Akt signaling.

Smart and colleagues (Nature, 2007) showed that Tβ4 could mobilize adult epicardial cells. These cells re-expressed embryonic programs and contributed to new vasculature after injury. This made Tβ4 a widely used tool for studying epicardial reactivation.

Caveats

Later work questioned how much epicardium-derived cells give rise to new cardiomyocytes, as opposed to vascular and fibroblast lineages. Results also depend on timing, delivery and model. Researchers should also note that fragment peptides do not necessarily reproduce every activity of full-length Tβ4.

References

  1. Bock-Marquette I, Saxena A, White MD, DiMaio JM, Srivastava D. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432:466–472.
  2. Smart N, Risebro CA, Melville AAD, et al. Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization. Nature. 2007;445:177–182.