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 LPA1-type receptor-mediated down-regulation 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 LPA1receptor, Rho kinase, and p300, leading to an acetylation of NFκB, which down-regulates the transcription of Sox10, MBP and MPZ genes.
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Nagasaki, Japan.
Ryoko
R
Tsukahara
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Nagasaki, Japan. Electronic address: ueda@nagasaki-u.ac.jp.
Hiroshi
H
Ueda
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D020868:Gene Silencing / Q000502:physiology*; D051379:Mice; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000502:physiology*
D016328:NF-kappa B; D049368:Receptors, Lysophosphatidic Acid; D054460:rho-Associated Kinases
Acetylation of NFκB; Demyelination; LPA