Neuregulin induces HaCaT keratinocyte migration via Rac1-mediated NADPH-oxidase activation.

Neuregulin (NRG), a member of the epidermal growth factor family, plays important roles in the development of the nervous system and heart, and in cancer progression. Recent reports have suggested that NRG is involved in wound healing in keratinocytes, although the cellular mechanisms remain unclear. Here, we showed that NRG treatment increased slingshot-1L (SSH-1L)-mediated cofilin dephosphorylation and activation in HaCaT keratinocytes. Additionally, Rac1 activation and NADPH-oxidase (Nox)-dependent reactive oxygen species (ROS) generation, both known to be upstream regulators of the SSH-cofilin pathway, were increased in NRG-stimulated HaCaT cells. Inhibition of Rac1 or Nox activity blocked NRG-induced cofilin activation and cell migration by HaCaT cells. Moreover, the effects of Rac1 on cofilin activation were dependent on Nox activity. These findings indicate that NRG-induced HaCaT cell migration via the ROS-SSH-1L-cofilin pathway is activated as a consequence of Rac1 and Nox activation.