Low-intensity pulsed ultrasound promotes proliferation and myelinating genes expression of Schwann cells through NRG1/ErbB signaling pathway

Abstract

Schwann cells (SCs) are the major component of myelin sheath in the peripheral nervous system, which are necessary in the development, function maintenance, and repair of peripheral nerves. This study aimed to investigate the potential mechanism of low-intensity pulsed ultrasound (LIPUS) affecting the proliferation and myelinating activity of SCs. Rat Schwann cell line RSC96 were cultured and exposed to LIPUS of different duty ratios (control, 20 %, 50 %, 80 %). Results demonstrated that LIPUS with a duty ratio of 50 % showing the maximal effect in facilitating proliferation of SCs. The expressions of Krox20 and myelin basic protein (MBP), the key molecules of SC myelination, and the potent inducer of myelination neuregulin 1 (NRG1) and its receptors ErbB2 and ErbB3 increased significantly by LIPUS. The reaction of these factors to LIPUS were both time- and duty ratio-dependent: namely LIPUS with higher duty ratios took effects when applied repeatedly over more consecutive days. These observations indicated that NRG1/ErbB signaling pathway might contribute to the effects of LIPUS on the proliferation and myelinating status of SCs, which could be one of the mechanisms in the protective role of LIPUS in nerve repair and regeneration. Our work provided novel insights for promising strategies of nerve repair therapy.