|
[原稿]
類視黃醇X受體γ信號促進中樞神經系統(tǒng)髓鞘再生
目前對中樞神經系統(tǒng)髓鞘再生的分子基礎的了解很少。我們獲得了大鼠中樞神經系統(tǒng)局灶性脫髓鞘后自發(fā)性髓鞘再生各階段的全面轉錄譜，結果發(fā)現(xiàn)，在髓鞘再生期間，編碼類視黃醇受體RXR－γ的轉錄物存在差異表達。在有髓鞘再生的大鼠組織以及活動性的有髓鞘再生的多發(fā)性硬化病變中，少突膠質譜系細胞能夠表達RXR－γ。通過RNA干擾或RXR特異的拮抗劑敲除RXR－γ嚴重抑制了培養(yǎng)物中的少突膠質細胞分化。在沒有RXR－γ的小鼠中，在脫髓鞘之后，成熟少突膠質前體細胞有效地修復了病變，但延遲分化為成熟少突膠質細胞。向脫髓鞘的小腦切片培養(yǎng)物和脫髓鞘后的衰老大鼠給予RXR激動劑9－順式－視黃酸能夠增加軸突髓鞘再生。我們的結果表明：RXR－γ是內源性少突膠質前體細胞分化和髓鞘再生的正性調節(jié)物，并且可能是中樞神經系統(tǒng)再生療法的藥理學作用靶的。
[譯文]
Retinoid X receptor gamma signaling accelerates CNS remyelination
The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-g were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-g in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-g by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-g, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-g is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS.
| 
京公網(wǎng)安備 11010502042637號