研究柑橘类黄酮对Rnd2敲除导致的少突胶质细胞系形态发生延缓的保护作用

IF 3.2 Q2 CLINICAL NEUROLOGY Neurology International Pub Date : 2023-12-26 DOI:10.3390/neurolint16010003
Shoya Fukatsu, Yuki Miyamoto, Yu Oka, Maki Ishibashi, Remina Shirai, Yuki Ishida, Shin Endo, Hironori Katoh, Junji Yamauchi
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引用次数: 0

摘要

最近的发现表明,大脑中细胞形态发生异常与少突胶质细胞等神经胶质细胞中控制信号转导的分子功能缺陷之间存在联系。Rnd2 就是这样一种分子,也是 Rho 家族单体 GTP 结合蛋白之一。尽管目前已知 Rnd2 的功能,但其与细胞形态发生和疾病状态有关的确切作用仍有待阐明。首先,我们利用经常被用作分化模型的 FBD-102b 细胞系,发现通过 rnd2 基因功能缺失发出的信号影响了少突胶质细胞样形态分化的调控。使用聚类规则间隔回文重复序列(CRISPR)/CasRx系统或RNA干扰敲除Rnd2,结果表明会减缓形态分化。其次,敲除 Rnd2 下游的信号分子 Prag1 或 Fyn 激酶也会减缓分化。Rnd2 或 Prag1 的敲除也会降低 Fyn 的磷酸化,而 Fyn 的磷酸化对其激活以及少突胶质细胞的分化和髓鞘化至关重要。值得注意的是,对少突胶质细胞和神经元具有保护作用的柑橘类黄酮--橙皮素能恢复由 Rnd2/Prag1/Fyn 敲除诱导的分化状态。在这里,我们发现通过Rnd2/Prag1/Fyn的信号传导参与了少突胶质细胞样形态分化的调控。敲除信号级联分子的影响可以通过橙皮素恢复,这突出了参与形态分化的一个重要分子结构。
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Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown.

Recent discoveries suggest links between abnormalities in cell morphogenesis in the brain and the functional deficiency of molecules controlling signal transduction in glial cells such as oligodendroglia. Rnd2 is one such molecule and one of the Rho family monomeric GTP-binding proteins. Despite the currently known functions of Rnd2, its precise roles as it relates to cell morphogenesis and disease state remain to be elucidated. First, we showed that signaling through the loss of function of the rnd2 gene affected the regulation of oligodendroglial cell-like morphological differentiation using the FBD-102b cell line, which is often utilized as a differentiation model. The knockdown of Rnd2 using the clustered regularly interspaced palindromic repeats (CRISPR)/CasRx system or RNA interference was shown to slow morphological differentiation. Second, the knockdown of Prag1 or Fyn kinase, a signaling molecule acting downstream of Rnd2, slowed differentiation. Rnd2 or Prag1 knockdown also decreased Fyn phosphorylation, which is critical for its activation and for oligodendroglial cell differentiation and myelination. Of note, hesperetin, a citrus flavonoid with protective effects on oligodendroglial cells and neurons, can recover differentiation states induced by the knockdown of Rnd2/Prag1/Fyn. Here, we showed that signaling through Rnd2/Prag1/Fyn is involved in the regulation of oligodendroglial cell-like morphological differentiation. The effects of knocking down the signaling cascade molecule can be recovered by hesperetin, highlighting an important molecular structure involved in morphological differentiation.

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来源期刊
Neurology International
Neurology International CLINICAL NEUROLOGY-
CiteScore
3.70
自引率
3.30%
发文量
69
审稿时长
11 weeks
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