Role of transforming growth factor-beta in peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits. Unlike in the central nervous system, damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells. However, axon regeneration and repair do not automatically result in the restoration of function, which is the ultimate therapeutic goal but also a major clinical challenge. Transforming growth factor (TGF) is a multifunctional cytokine that regulates various biological processes including tissue repair, embryo development, and cell growth and differentiation. There is accumulating evidence that TGF-beta family proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells; recruiting specific immune cells; controlling the permeability of the blood-nerve barrier, thereby stimulating axon growth; and inhibiting remyelination of regenerated axons. TGF-beta has been applied to the treatment of peripheral nerve injury in animal models. In this context, we review the functions of TGF-beta in peripheral nerve regeneration and potential clinical applications.