Myelin-related gene silencing mediated by LPA1 - Rho/ROCK signaling is correlated to acetylation of NFκB in S16 Schwann cells

Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA(1)-type receptor-mediated downregulation of myelin-related molecules, such as MBP and MPZ. In this study using S16 mature-type Schwann cells, we found that LPA-induced down-regulation of myelin-related genes is attributed by the activation of LPA(1) receptor, Rho kinase, and p300, leading to an acetylation of NF kappa B, which downregulates the transcription of Sox10, MBP and MPZ genes. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.