Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury
العنوان: | Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury |
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المؤلفون: | Haipeng Zhang, Yi Cui, Bing Chen, Weiwei Xue, Jiayin Li, Yannan Zhao, Weiyuan Liu, Yanyun Yin, Zhifeng Xiao, Jianwu Dai, Ya Shi, Bai Xu, Yongheng Fan |
المصدر: | Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-12 (2021) Stem Cell Research & Therapy |
بيانات النشر: | BMC, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, Medicine (General), Medicine (miscellaneous), Spinal cord injury, QD415-436, Epothilone, Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, R5-920, Neural Stem Cells, Downregulation and upregulation, RNA interference, Apol8, medicine, Animals, Spinal Cord Injuries, Neurons, Research, Cell Differentiation, Recovery of Function, Cell Biology, Retrograde tracing, Neural stem cell, Up-Regulation, Cell biology, Blot, Transplantation, 030104 developmental biology, Spinal Cord, nervous system, Neuronal differentiation, Epothilones, Molecular Medicine, Epothilone D, Stem cell, 030217 neurology & neurosurgery, medicine.drug |
الوصف: | Background Microtubule-stabilizing agents have been demonstrated to modulate axonal sprouting during neuronal disease. One such agent, Epothilone D, has been used to treat spinal cord injury (SCI) by promoting axonal sprouting at the lesion site after SCI. However, the role of Epothilone D in the differentiation of neural stem cells (NSCs) in SCI repair is unknown. In the present study, we mainly explored the effects and mechanisms of Epothilone D on the neuronal differentiation of NSCs and revealed a potential new SCI treatment. Methods In vitro differentiation assays, western blotting, and quantitative real-time polymerase chain reaction were used to detect the effects of Epothilone D on NSC differentiation. Retrograde tracing using a pseudotyped rabies virus was then used to detect neuronal circuit construction. RNA sequencing (RNA-Seq) was valuable for exploring the target gene involved in the neuronal differentiation stimulated by Epothilone D. In addition, lentivirus-induced overexpression and RNA interference technology were applied to demonstrate the function of the target gene. Last, an Apol8-NSC-linear ordered collagen scaffold (LOCS) graft was prepared to treat a mouse model of SCI, and functional and electrophysiological evaluations were performed. Results We first revealed that Epothilone D promoted the neuronal differentiation of cultured NSCs and facilitated neuronal relay formation in the injured site after SCI. Furthermore, the RNA-Seq results demonstrated that Apol8 was upregulated during Epothilone D-induced neuronal relay formation. Lentivirus-mediated Apol8 overexpression in NSCs (Apol8-NSCs) promoted NSC differentiation toward neurons, and an Apol8 interference assay showed that Apol8 had a role in promoting neuronal differentiation under the induction of Epothilone D. Last, Apol8-NSC transplantation with LOCS promoted the neuronal differentiation of transplanted NSCs in the lesion site as well as synapse formation, thus improving the motor function of mice with complete spinal cord transection. Conclusions Epothilone D can promote the neuronal differentiation of NSCs by upregulating Apol8, which may provide a promising therapeutic target for SCI repair. |
اللغة: | English |
تدمد: | 1757-6512 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::edf9d357b44501b59f990f8f464c7116 https://doaj.org/article/b7b84df762304a75a34f86682a2e8505 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....edf9d357b44501b59f990f8f464c7116 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 17576512 |
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