RESUMO
Increases in Rattus norvegicus ribonuclease/angiogenin inhibitor 1 (Rnh1) are observed in rat primary neuron injury and/or the regeneration process and in differentiated oligodendrocytes. However, the roles of Rnh1 in the central nervous system are still largely unexplored. RhoA is an important signaling protein that has been implicated in oligodendrocyte differentiation and myelination. We demonstrate enhanced differentiation and myelination of oligodendrocytes mediated by Rnh1 in vitro. We further show that Rnh1 is expressed in oligodendrocyte precursors and oligodendrocytes. Importantly, Rnh1 strongly affects oligodendrocyte differentiation through RhoA-ROCK signaling. Moreover, changes in Rnh1 expression in oligodendrocytes regulates the expression and phosphorylation of Fyn, a regulator of RhoA activity. Finally, Rnh1 promotes myelination in vitro. These results show that Rnh1-mediated RhoA inactivation enhances the differentiation and myelination in oligodendrocytes. Overall, Rnh1 might contribute to oligodendrocyte differentiation and myelination processes in vitro.
Assuntos
Proteínas de Transporte/metabolismo , Bainha de Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Oligodendroglia/metabolismo , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Proteínas de Transporte/genética , Diferenciação Celular , Células Cultivadas , Regulação da Expressão Gênica/fisiologia , Bainha de Mielina/genética , Proteínas do Tecido Nervoso/genética , Oligodendroglia/citologia , Fosforilação/fisiologia , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Ratos , Ratos Wistar , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/genéticaRESUMO
SCIRR39 is an identified upregulated gene in rat primary neuron injury and/or regeneration process. However, roles of SCIRR39 in the regeneration of central nervous system (CNS) injury are still largely unexplored. Using real-time quantitative PCR and Western blotting, SCIRR39 expression was detected in oligodendrocyte precursor cells (OPCs) and oligodendrocytes. Moreover, the results from cell proliferation and cell cycle indicated that SCIRR39 inhibited OPCs proliferation and induced cell cycle arrest in G0/G1 and G2/M phases. Importantly, SCIRR39 positively regulated OPC differentiation and the expression of myelin basic protein. We also examined the effect of SCIRR39 on expression of myelin-associated inhibitory factors, including myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and Nogo A. Nogo A level was markedly regulated by SCIRR39 overexpression or knockdown in oligodendrocytes and cortical neurons co-cultures, while the expression of MAG and OMgp was not obviously changed by SCIRR39 overexpression or knockdown. Taken together, our results indicate the important role of SCIRR39 either in OPC differentiation or in axon myelination, and may provide a new therapeutic target for the treatment of CNS injury.
