Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration

Transforming growth factor beta (TGF) signalling is essential for wound healing, including both non-specific scar formation and tissue-specific regeneration. Specific TGF isoforms and downstream mediators of canonical and non-canonical signalling play different roles in each of these processes. Here we review the role of TGF signalling during tissue repair, with a particular focus on the prototypic isoforms TGF1, TGF2, and TGF3. We begin by introducing TGF signalling and then discuss the role of these growth factors and their key downstream signalling mediators in determining the balance between scar formation and tissue regeneration. Next we discuss examples of the pleiotropic roles of TGF ligands during cutaneous wound healing and blastema-mediated regeneration, and how inhibition of the canonical signalling pathway (using small molecule inhibitors) blocks regeneration. Finally, we review various TGF-targeting therapeutic strategies that hold promise for enhancing tissue repair.