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...
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MDPI AG
2023-12-01
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| Series: | Neurology International |
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| Online Access: | https://www.mdpi.com/2035-8377/16/1/3 |
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| author | Shoya Fukatsu Yuki Miyamoto Yu Oka Maki Ishibashi Remina Shirai Yuki Ishida Shin Endo Hironori Katoh Junji Yamauchi |
| author_facet | Shoya Fukatsu Yuki Miyamoto Yu Oka Maki Ishibashi Remina Shirai Yuki Ishida Shin Endo Hironori Katoh Junji Yamauchi |
| author_sort | Shoya Fukatsu |
| collection | DOAJ |
| description | 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 <i>rnd2</i> 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. |
| first_indexed | 2024-03-07T22:19:26Z |
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| institution | Directory Open Access Journal |
| issn | 2035-8377 |
| language | English |
| last_indexed | 2024-03-07T22:19:26Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Neurology International |
| spelling | doaj.art-f1d0953ed0044ceabf31fadc9f4588942024-02-23T15:29:38ZengMDPI AGNeurology International2035-83772023-12-01161336110.3390/neurolint16010003Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 KnockdownShoya Fukatsu0Yuki Miyamoto1Yu Oka2Maki Ishibashi3Remina Shirai4Yuki Ishida5Shin Endo6Hironori Katoh7Junji Yamauchi8Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanLaboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanPersonal Health Care Division, Hayashibara Co., Ltd., Okayama 702-8006, JapanPersonal Health Care Division, Hayashibara Co., Ltd., Okayama 702-8006, JapanLaboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanPersonal Health Care Division, Hayashibara Co., Ltd., Okayama 702-8006, JapanPersonal Health Care Division, Hayashibara Co., Ltd., Okayama 702-8006, JapanDepartment of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, Osaka 599-8531, JapanLaboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanRecent 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 <i>rnd2</i> 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.https://www.mdpi.com/2035-8377/16/1/3monomeric GTP-binding proteinsphosphotransferasessignal transductiondiseaseflavonoidRNA |
| spellingShingle | Shoya Fukatsu Yuki Miyamoto Yu Oka Maki Ishibashi Remina Shirai Yuki Ishida Shin Endo Hironori Katoh Junji Yamauchi Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown Neurology International monomeric GTP-binding proteins phosphotransferases signal transduction disease flavonoid RNA |
| title | Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown |
| title_full | Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown |
| title_fullStr | Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown |
| title_full_unstemmed | Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown |
| title_short | Investigating the Protective Effects of a Citrus Flavonoid on the Retardation Morphogenesis of the Oligodendroglia-like Cell Line by Rnd2 Knockdown |
| title_sort | investigating the protective effects of a citrus flavonoid on the retardation morphogenesis of the oligodendroglia like cell line by rnd2 knockdown |
| topic | monomeric GTP-binding proteins phosphotransferases signal transduction disease flavonoid RNA |
| url | https://www.mdpi.com/2035-8377/16/1/3 |
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